- FGF23 induces left ventricular hypertrophy
Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA
J Clin Invest 121:4393-408. 2011
..These results unveil a klotho-independent, causal role for FGF23 in the pathogenesis of LVH and suggest that chronically elevated FGF23 levels contribute directly to high rates of LVH and mortality in individuals with CKD...
- Vascular Klotho deficiency potentiates the development of human artery calcification and mediates resistance to fibroblast growth factor 23
Brigham and Women s Hospital, Harvard Medical School, Room 120, 41 Ave Louis Pasteur, Boston, MA 02115, USA
Circulation 125:2243-55. 2012
..FGF-23 levels rise in chronic kidney disease (CKD) despite progression of accelerated vascular calcification. There are currently conflicting data on whether FGF-23 may exhibit direct vasculoprotective effects in CKD...
- Suppression of aging in mice by the hormone Klotho
Department of Pathology, University of Texas UT Southwestern Medical Center at Dallas, 5323 Harry Hines Bouleuvard, Dallas, TX 75390 9072, USA
Science 309:1829-33. 2005
..Klotho protein may function as an anti-aging hormone in mammals...
- Klotho converts canonical FGF receptor into a specific receptor for FGF23
Pharmaceutical Research Laboratories, Kirin Brewery Co, Ltd, 3 Miyahara, Takasaki, Gunma 370 1295, Japan
Nature 444:770-4. 2006
..Thus, the concerted action of Klotho and FGFR1(IIIc) reconstitutes the FGF23 receptor. These findings provide insights into the diversity and specificity of interactions between FGF and FGF receptors...
- Multilevel interactions between ethylene and auxin in Arabidopsis roots
Anna N Stepanova
Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695, USA
Plant Cell 19:2169-85. 2007
..This model not only implies existence of several levels of interaction but also provides a likely explanation for the strong ethylene response defects observed in auxin mutants...
- Klotho deficiency causes vascular calcification in chronic kidney disease
Ming Chang Hu
Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 8885, USA
J Am Soc Nephrol 22:124-36. 2011
..Klotho ameliorates vascular calcification by enhancing phosphaturia, preserving glomerular filtration, and directly inhibiting phosphate uptake by vascular smooth muscle. Replacement of Klotho may have therapeutic potential for CKD...
- Regulation, function and clinical significance of heparanase in cancer metastasis and angiogenesis
Cancer and Vascular Biology Research Center, The Bruce Rappaport Faculty of Medicine, Technion, P O Box 9649, Haifa 31096, Israel
Int J Biochem Cell Biol 38:2018-39. 2006
..We also discuss clinical aspects and strategies for the development of heparanase inhibitors...
- Regulation of fibroblast growth factor-23 signaling by klotho
Department of Pathology, Pediatrics, and Internal Medicine and Applied Genomics, Genzyme Corporation, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
J Biol Chem 281:6120-3. 2006
..Thus, Klotho functions as a cofactor essential for activation of FGF signaling by FGF23...
- Angiotensin II blockade upregulates the expression of Klotho, the anti-ageing gene, in an experimental model of chronic cyclosporine nephropathy
Hye Eun Yoon
Division of Nephrology, Department of Internal Medicine, Incheon St Mary s Hospital, College of Medicine, The Catholic University of Korea, Incheon, South Korea
Nephrol Dial Transplant 26:800-13. 2011
..It is suggested that activation of renin-angiotensin system (RAS) or oxidative stress suppresses Klotho in the kidney. This study evaluated the association between Klotho expression and RAS in cyclosporine (CsA)-induced renal injury...
- Klotho inhibits transforming growth factor-beta1 (TGF-beta1) signaling and suppresses renal fibrosis and cancer metastasis in mice
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
J Biol Chem 286:8655-65. 2011
..These results have raised the possibility that secreted Klotho may function as an endogenous anti-EMT factor by inhibiting multiple growth factor signaling pathways simultaneously...
- Severely reduced production of klotho in human chronic renal failure kidney
Department of Pathology and Tumor Biology, Kyoto University Graduate School of Medicine, Konoe cho, Yoshida, Sakyo ku, Kyoto, 606 8501, Japan
Biochem Biophys Res Commun 280:1015-20. 2001
..These results suggest that the decrease in kl gene expression in CRF patients may underlie the deteriorating process of multiple complications in the CRF patients...
- Development of series of gateway binary vectors, pGWBs, for realizing efficient construction of fusion genes for plant transformation
Department of Molecular and Functional Genomics, Center for Integrated Research in Science, Shimane University, 1060 Nishikawatsu, Matsue, Japan
J Biosci Bioeng 104:34-41. 2007
..The reporters employable in this system are beta-glucuronidase (GUS), synthetic green fluorescent protein with S65T mutation (sGFP), luciferase (LUC), enhanced yellow ..
- Vitamin D receptor agonists increase klotho and osteopontin while decreasing aortic calcification in mice with chronic kidney disease fed a high phosphate diet
Wei Ling Lau
Department of Nephrology, University of Washington, Seattle, Washington 98195, USA
Kidney Int 82:1261-70. 2012
..Thus, klotho and osteopontin were upregulated by VDRA therapy in chronic kidney disease, independent of changes in serum parathyroid hormone and calcium...
- Regulation and function of the FGF23/klotho endocrine pathways
University of Tennessee Health Science Center, Memphis, Tennessee, USA
Physiol Rev 92:131-55. 2012
..This review discusses the known and emerging functions of FGF23, its regulation in response to systemic and local signals, as well as the implications of FGF23 in different pathological and physiological contexts...
- Eradication of solid human breast tumors in nude mice with an intravenously injected light-emitting oncolytic vaccinia virus
Genelux Corporation, San Diego Science Center, San Diego, California 92109, USA
Cancer Res 67:10038-46. 2007
..cassettes (encoding Renilla luciferase-Aequorea green fluorescent protein fusion, beta-galactosidase, and beta-glucuronidase) into the F14...
- Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule
Ming Chang Hu
Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390 8885, USA
FASEB J 24:3438-50. 2010
..Transport inhibition can be mimicked by recombinant beta-glucuronidase and is associated with proteolytic degradation and reduced surface NaPi-2a...
- KL1 internal repeat mediates klotho tumor suppressor activities and inhibits bFGF and IGF-I signaling in pancreatic cancer
Institute of Oncology, The Chaim Sheba Medical Center, Ramat Gan, Tel Aviv, Israel
Clin Cancer Res 17:4254-66. 2011
..Klotho is expressed in the normal pancreas and both the IGF-I and FGF pathways are involved in pancreatic cancer development. We, therefore, undertook to study the expression and activity of klotho in pancreatic cancer...
- Heparanase and syndecan-1 interplay orchestrates fibroblast growth factor-2-induced epithelial-mesenchymal transition in renal tubular cells
Department of Experimental Biomedical Sciences, University of Padova, 35122 Padova, Italy
J Biol Chem 287:1478-88. 2012
..In conclusion, heparanase plays a role in the tubular-interstitial compartment favoring the FGF-2-dependent EMT of tubular cells. Hence, heparanase is an interesting pharmacological target for the prevention of renal fibrosis...
- The heparanase system and tumor metastasis: is heparanase the seed and soil?
Cancer and Vascular Biology Research Center, Bruce Rappaport Faculty of Medicine, Technion, P O Box 9649, Haifa, 31096, Israel
Cancer Metastasis Rev 30:253-68. 2011
..In addition, cathepsin L is held responsible for processing and activation of heparanase, an endo-β-glucuronidase capable of cleaving heparan sulfate side chains of heparan sulfate proteoglycans, activity that is strongly ..
- Decreased expression of klotho gene in uremic atherosclerosis in apolipoprotein E-deficient mice
Department of Cardiovasology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China
Biochem Biophys Res Commun 391:261-6. 2010
..These results suggested that CRF favored atherosclerosis in apo-E(-/-) mice and uremic atherosclerosis was accompanied by down-regulation of klotho expression...
- Tumor suppressor p53 regulates heparanase gene expression
Department of Oncology, Hadassah University Medical Center, Jerusalem, Israel
Oncogene 25:3939-47. 2006
- Role of Klotho in aging, phosphate metabolism, and CKD
George B John
Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 9072, USA
Am J Kidney Dis 58:127-34. 2011
..This review focuses on the current understanding of Klotho protein function, with emphasis on its potential involvement in the pathophysiologic process of CKD...
- Heparanase is essential for the development of diabetic nephropathy in mice
Sharett Institute, Hadassah Hebrew University Medical Center, Jerusalem, Israel
Diabetes 61:208-16. 2012
..Our results collectively underscore the crucial role of heparanase in the pathogenesis of DN and its potential as a highly relevant target for therapeutic interventions in patients with DN...
- Cell surface heparan sulfate released by heparanase promotes melanoma cell migration and angiogenesis
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin 53706, USA
J Cell Biochem 106:200-9. 2009
..The enzyme acts as an endo-beta-D-glucuronidase resulting in HS fragments of discrete molecular weight size...
- Heparanase-enhanced shedding of syndecan-1 by myeloma cells promotes endothelial invasion and angiogenesis
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Blood 115:2449-57. 2010
- Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17
Ci Di Chen
Departments of Biochemistry, Pharmacology, and Medicine, Boston University School of Medicine, Boston, MA 02118, USA
Proc Natl Acad Sci U S A 104:19796-801. 2007
..Insulin enhances KL shedding without increasing ADAM10 and ADAM17 mRNA and protein levels, suggesting that it acts by stimulating their proteolytic activities...
- Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein
Division of Molecular Genetics, National Institute of Neuroscience, NCNP, Tokyo, Japan
Biochem Biophys Res Commun 242:626-30. 1998
..Expression of the putative secreted form predominates over that of the membrane form. The present study provides fundamental information necessary for further analyses of the human kl gene and its functions...
- The parathyroid is a target organ for FGF23 in rats
Iddo Z Ben-Dov
Minerva Center for Calcium and Bone Metabolism, Nephrology Services, Hadassah Hebrew University Medical Center, Jerusalem, Israel
J Clin Invest 117:4003-8. 2007
..These data indicate that FGF23 acts directly on the parathyroid through the MAPK pathway to decrease serum PTH. This bone-parathyroid endocrine axis adds a new dimension to the understanding of mineral homeostasis...
- Identification of sulfated oligosaccharide-based inhibitors of tumor growth and metastasis using novel in vitro assays for angiogenesis and heparanase activity
C R Parish
Division of Immunology and Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra
Cancer Res 59:3433-41. 1999
..Acute hematogenous metastasis assays also demonstrated that PI-88 was a potent (>90%) inhibitor of blood-borne metastasis. Thus, by the use of novel in vitro screening procedures, we have identified a promising antitumor agent...
- Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606 8501, Japan
Mol Endocrinol 17:2393-403. 2003
..These observations suggest that klotho may participate in a negative regulatory circuit of the vitamin D endocrine system, through the regulation of 1alpha-hydroxylase gene expression...
- Immunohistochemical localization of Klotho protein in brain, kidney, and reproductive organs of mice
Shun Ai Li
Department of Neuroscience, Okayama University Graduate School of Medicine and Dentistry, 2 5 1 Shikata cho, Okayama 700 8558, Japan
Cell Struct Funct 29:91-9. 2004
..Thus, Klotho proteins not only function as a humoral factor, but also are implicated in hormonal regulation, which may explain why mutation of klotho gene results in a variety of phenotypes...
- In vivo genetic evidence for klotho-dependent, fibroblast growth factor 23 (Fgf23) -mediated regulation of systemic phosphate homeostasis
Department of Developmental Biology, Harvard School of Dental Medicine, 188 Longwood Ave, Boston, MA 02115, USA
FASEB J 23:433-41. 2009
..Together, these results provide compelling evidence that Fgf23 does not have a klotho-independent role in the regulation of systemic phosphate and vitamin D homeostasis...
- Secreted Klotho protein in sera and CSF: implication for post-translational cleavage in release of Klotho protein from cell membrane
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto 606 8501, Japan
FEBS Lett 565:143-7. 2004
..The secreted as well as the membrane-bound Klotho proteins were suggested to form oligomerized complex. These results delineate post-translation processing of Klotho and possible regulatory mechanisms for secretion of Klotho in vivo...
- Klotho prevents renal calcium loss
R Todd Alexander
Department of Physiology, Nijmegen Centre for Molecular Life Sciences, 6500 HB Nijmegen, The Netherlands
J Am Soc Nephrol 20:2371-9. 2009
..This highlights the importance of klotho to the prevention of renal Ca(2+) loss, secondary hypervitaminosis D, osteopenia, and nephrocalcinosis...
- betaKlotho is required for fibroblast growth factor (FGF) 21 signaling through FGF receptor (FGFR) 1c and FGFR3c
Signaling Molecules Research Laboratory, National Institute of Advanced Industrial Science and Technology, Central 6, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8566, Japan
Mol Endocrinol 22:1006-14. 2008
..It is thus suggested that betaKlotho expression is a crucial determinant of the FGF21 specificity of the target cells upon which it acts in an endocrine fashion...
- Circulating α-klotho levels in CKD and relationship to progression
Hyoung Rae Kim
Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea
Am J Kidney Dis 61:899-909. 2013
..However, circulating α-klotho levels in human chronic kidney disease (CKD) and the relationship to progression are unknown...
- In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage
Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan
Hypertension 39:838-43. 2002
- Increased bone volume and correction of HYP mouse hypophosphatemia in the Klotho/HYP mouse
Catherine A Brownstein
Department of Genetics, Yale University School of Medicine, 333 Cedar Street, SHM I 308, New Haven, Connecticut 06510, USA
Endocrinology 151:492-501. 2010
- Establishment of sandwich ELISA for soluble alpha-Klotho measurement: Age-dependent change of soluble alpha-Klotho levels in healthy subjects
Antibody Research Laboratories, Kyowa Hakko Kirin Co Ltd, Tokyo 194 8533, Japan
Biochem Biophys Res Commun 398:513-8. 2010
..Although the importance of transmembrane-type alphaKl has been demonstrated, less is known regarding the physiological importance of soluble-type alphaKl (salphaKl) in circulation...
- Liver-specific activities of FGF19 require Klotho beta
Benjamin C Lin
Department of Molecular Oncology, Genentech Inc, South San Francisco, CA 94080, USA
J Biol Chem 282:27277-84. 2007
..The tissue-specific activity of FGF19 supports the unique intersection of KLB and FGFR4 distribution in liver. These studies define KLB as a novel FGFR4 coreceptor required for FGF19 liver specific functions...
- Heparanase expression in human colorectal cancer and its relationship to tumor angiogenesis, hematogenous metastasis, and prognosis
First Department of Surgery, University of Fukui, Matsuoka cho, Yoshida gun, Fukui, Japan
J Surg Oncol 87:174-81. 2004
..Heparanase is considered to play an important role in tumor invasion and hematogenous metastasis. The aim of this study was to determine the expression of heparanase in colorectal cancer to evaluate its prognostic value...
- Molecular insights into the klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily members
Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
Mol Cell Biol 27:3417-28. 2007
..Klotho/betaKlotho have evolved as a compensatory mechanism for the poor ability of heparin/heparan sulfate to promote binding of FGF19, -21, and -23 to their cognate receptors...
- Proteoglycans in health and disease: new concepts for heparanase function in tumor progression and metastasis
Cancer and Vascular Biology Research Center, Rappaport Faculty of Medicine, Haifa, Israel
FEBS J 277:3890-903. 2010
Heparanase is an endo-β-D-glucuronidase capable of cleaving heparan sulfate side chains at a limited number of sites, yielding heparan sulfate fragments of still appreciable size...
- Klotho: a tumor suppressor and a modulator of the IGF-1 and FGF pathways in human breast cancer
Institute of Oncology Chaim Sheba Medical Center, Ramat Gan, Israel
Oncogene 27:7094-105. 2008
..These data suggest klotho as a potential tumor suppressor and identify it as an inhibitor of the IGF-1 pathway and activator of the FGF pathway in human breast cancer...
- Small RNA interference-mediated gene silencing of heparanase abolishes the invasion, metastasis and angiogenesis of gastric cancer cells
Department of Surgery, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
BMC Cancer 10:33. 2010
..The aim of this study is to determine whether silencing of heparanase expression can abolish the malignant characteristics of gastric cancer cells...
- MicroRNA-1258 suppresses breast cancer brain metastasis by targeting heparanase
Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA
Cancer Res 71:645-54. 2011
- T-DNA insertional mutagenesis for activation tagging in rice
Dong Hoon Jeong
Department of Life Science and National Research Laboratory of Plant Functional Genomics, Pohang University of Science and Technology, Pohang 790 784, Republic of Korea
Plant Physiol 130:1636-44. 2002
..The binary vector contains the promoterless beta-glucuronidase (GUS) reporter gene next to the right border...
- Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis
Department of Oncology, Hadassah Hebrew University Hospital, Jerusalem, Israel
Nat Med 5:793-802. 1999
..Cloning of the heparanase gene enables the development of specific molecular probes for early detection and treatment of cancer metastasis and autoimmune disorders...
- Isolated C-terminal tail of FGF23 alleviates hypophosphatemia by inhibiting FGF23-FGFR-Klotho complex formation
Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
Proc Natl Acad Sci U S A 107:407-12. 2010
..We propose that peptides derived from the C-terminal tail of FGF23 or peptidomimetics and small-molecule organomimetics of the C-terminal tail can be used as therapeutics to treat renal phosphate wasting...
- Klotho suppresses TNF-alpha-induced expression of adhesion molecules in the endothelium and attenuates NF-kappaB activation
Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565 0871, Japan
Endocrine 35:341-6. 2009
..These results suggest that Klotho suppresses TNF-alpha-induced expression of adhesion molecules and NF-kappaB activation. Klotho may have a role in the modulation of endothelial inflammation...
- Intraventricular brain injection of adeno-associated virus type 1 (AAV1) in neonatal mice results in complementary patterns of neuronal transduction to AAV2 and total long-term correction of storage lesions in the brains of beta-glucuronidase-deficient mi
Marco A Passini
Department of Pathobiology and Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Virol 77:7034-40. 2003
..The number of cells positive for a vector-encoded secreted enzyme (beta-glucuronidase) was notably greater and more widespread in AAV1-injected brains...
- The Klotho gene family as a regulator of endocrine fibroblast growth factors
Department of Hygiene and Public Health I, Tokyo Women s Medical University, 8 1, Kawada cho, Shinjuku ku, Tokyo 162 8666, Japan
Mol Cell Endocrinol 299:72-8. 2009
..This review summarizes recent progress in understanding of Klotho and betaKlotho function in the regulation of tissue-specific metabolic activity of the endocrine fibroblast growth factors (FGF19, FGF21, and FGF23)...
- Reversal of mineral ion homeostasis and soft-tissue calcification of klotho knockout mice by deletion of vitamin D 1alpha-hydroxylase
Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA
Kidney Int 75:1166-72. 2009
Changes in the expression of klotho, a beta-glucuronidase, contribute to the development of features that resemble those of premature aging, as well as chronic renal failure...
- Relevant use of Klotho in FGF19 subfamily signaling system in vivo
Ken ichi Tomiyama
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Sakyo ku, Kyoto 606 8501, Japan
Proc Natl Acad Sci U S A 107:1666-71. 2010
..One-to-one functional interactions such as alpha-Klotho/FGF23, beta-Klotho/FGF15 (humanFGF19), and undefined cofactor/FGF21 would result in tissue-specific signal transduction of the FGF19 subfamily...
- Klotho is associated with VEGF receptor-2 and the transient receptor potential canonical-1 Ca2+ channel to maintain endothelial integrity
Department of Cardiovascular and Renal Medicine, Kyoto Prefectural University of Medicine, Kyoto 602 8566, Japan
Proc Natl Acad Sci U S A 107:19308-13. 2010
..These findings provide evidence that Klotho protein is associated with VEGFR-2/TRPC-1 in causing cointernalization, thus regulating TRPC-1-mediated Ca(2+) entry to maintain endothelial integrity...
- A new targeting approach for breast cancer gene therapy using the heparanase promoter
Division of Human Gene Therapy, Department of Medicine, Gene Therapy Center, 901 19th Street South, BMR2 508, University of Alabama at Birmingham, Birmingham, AL 35294 2172, USA
Cancer Lett 240:114-22. 2006
..We conclude that the HPR pathway is a promising target for the development of breast cancer directed gene therapy strategies...
- Heparanase activity in alveolar and embryonal rhabdomyosarcoma: implications for tumor invasion
Department of Experimental Biomedical Sciences, University of Padova, 35121 Padova, Italy
BMC Cancer 9:304. 2009
..This feature is influenced by several biological molecules, including soluble factors secreted by tumor cells, such as heparanase (HPSE). HPSE is an endo-beta-D-glucuronidase that cleaves heparan sulphate proteoglycans.
- Dietary and genetic evidence for phosphate toxicity accelerating mammalian aging
Department of Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, USA
FASEB J 24:3562-71. 2010
..The results of our dietary and genetic manipulation studies provide in vivo evidence for phosphate toxicity accelerating the aging process and suggest a novel role for phosphate in mammalian aging...
- Klotho reduces apoptosis in experimental ischaemic acute kidney injury via HSP-70
Department of Medicine IV, Tokyo Women s Medical University, Tokyo, Japan
Nephrol Dial Transplant 25:60-8. 2010
- Endothelial dysfunction in the klotho mouse and downregulation of klotho gene expression in various animal models of vascular and metabolic diseases
Second Department of Internal Medicine, Gunma University School of Medicine, Japan
Cell Mol Life Sci 57:738-46. 2000
..The Klotho protein itself, or its metabolites, promotes endothelial NO production in aorta as well as arterioles, and klotho mRNA in kidney is downregulated under sustained circulatory stress...
- Serum soluble α-klotho in hemodialysis patients
Division of Kidney and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
Clin Nephrol 77:347-51. 2012
..The extracellular domain of klotho is cleaved and released into various extracellular fluids, such as blood, urine, and cerebrospinal fluid, as soluble α-klotho (sαKl)...
- The role of glycosylation and phosphorylation in the expression of active human beta-glucuronidase
J M Shipley
Edward A Doisy Department of Biochemistry and Molecular Biology, St Louis University School of Medicine, Missouri 63104
J Biol Chem 268:12193-8. 1993
..site-directed mutagenesis to observe the effect of eliminating selective glycosylation sites from human beta-glucuronidase on enzyme sorting...
- Plasma klotho and cardiovascular disease in adults
Richard D Semba
Department of Ophthalmology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland, USA
J Am Geriatr Soc 59:1596-601. 2011
..To determine whether plasma klotho, a recently discovered hormone that has been implicated in atherosclerosis, is related to prevalent cardiovascular disease (CVD) in adults...
- Validation of an immunoassay for soluble Klotho protein: decreased levels in diabetes and increased levels in chronic kidney disease
Department of Pathology and Immunology, Texas Children s Hospital and Baylor College of Medicine, Houston, USA
Am J Clin Pathol 137:479-85. 2012
..5%; P < .001). We also documented significantly higher levels of Klotho with CKD. Thus, we validated an assay for Klotho and made the novel observation that levels are decreased in diabetes and increased in CKD...
- Klotho lacks a vitamin D independent physiological role in glucose homeostasis, bone turnover, and steady-state PTH secretion in vivo
Institute of Physiology, Pathophysiology and Biophysics, Department of Biomedical Sciences, University of Veterinary Medicine, Vienna, Austria
PLoS ONE 7:e31376. 2012
..In conclusion, our findings cast doubt on a physiologically relevant vitamin D and Fgf23 independent function of Klotho in the regulation of glucose metabolism, bone turnover, and steady-state PTH secretion in vivo...
- Cloning of the canine beta-glucuronidase cDNA, mutation identification in canine MPS VII, and retroviral vector-mediated correction of MPS VII cells
James A Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA
Genomics 48:248-53. 1998
..VII (MPS VII) is an inherited disease resulting from deficient activity of the lysosomal acid hydrolase beta-glucuronidase (GUSB) and has been reported in humans, mice, cats, and dogs...
- Reduced Klotho expression level in kidney aggravates renal interstitial fibrosis
Dept of Medicine IV, Tokyo Women s Medical Univ, 8 1 Kawada cho, Shinjuku City, Tokyo, Japan 162 8666
Am J Physiol Renal Physiol 302:F1252-64. 2012
..Taken together, renal fibrosis can trigger a deterioration spiral of Klotho expression, which may be involved in the pathophysiology of CKD progression...
- Decreased renal α-Klotho expression in early diabetic nephropathy in humans and mice and its possible role in urinary calcium excretion
First Department of Internal Medicine, Nara Medical University, Kashihara, Japan
Kidney Int 81:539-47. 2012
..Thus, α-Klotho expression was decreased in distal convoluted tubules in diabetic nephropathy in humans and mice. Renal loss of α-Klotho may affect urinary calcium excretion in early diabetic nephropathy...
- An artificial miRNA against HPSE suppresses melanoma invasion properties, correlating with a down-regulation of chemokines and MAPK phosphorylation
Department of Dermatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People s Republic of China
PLoS ONE 7:e38659. 2012
..Furthermore, miRNA-based RNAi was also a powerful tool for gene function study...
- Soluble serum Klotho in diabetic nephropathy: relationship to VEGF-A
Ina Maria Kacso
University of Medicine and Pharmacy Iuliu Hatieganu Cluj Napoca, Department of Nephrology, Romania
Clin Biochem 45:1415-20. 2012
..Serum Klotho is a yet poorly explored biomarker. We describe, for the first time to our knowledge, serum Klotho in diabetic patients with CKD and its relationship to vascular endothelial growth factor A (VEGF-A)...
- Klotho expression in epithelial ovarian cancer and its association with insulin-like growth factors and disease progression
Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06520 8034, USA
Cancer Invest 26:185-92. 2008
..In conclusion, Klotho expression is associated with epithelial ovarian cancer progression, and the protein may serve as an independent marker for ovarian cancer prognosis. Klotho's role in cancer warrants further elucidation...
- A decreased level of serum soluble Klotho is an independent biomarker associated with arterial stiffness in patients with chronic kidney disease
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
PLoS ONE 8:e56695. 2013
..However, it is unclear whether the serum Klotho levels are associated with signs of vascular dysfunction such as arterial stiffness, a major determinant of prognosis, in human subjects with chronic kidney disease (CKD)...
- Characteristics of urinary and serum soluble Klotho protein in patients with different degrees of chronic kidney disease
Division of Nephrology, Department of Internal Medicine, Jichi Medical University, 3311 1 Yakushiji, Shimotsuke shi, Tochigi, 329 0498, Japan
BMC Nephrol 13:155. 2012
..The purpose of the present study was to characterize the relationship between the soluble Klotho level and renal function in patients with various degrees of chronic kidney disease (CKD)...
- Secreted Klotho and FGF23 in chronic kidney disease Stage 1 to 5: a sequence suggested from a cross-sectional study
Institute of Physiology and Zurich Center for Integrative Human Physiology, Zurich, Switzerland
Nephrol Dial Transplant 28:352-9. 2013
..FGF23 levels have been shown to increase early in chronic kidney disease (CKD); however, the corresponding soluble Klotho levels at the different CKD stages are not known...
- Urinary heparanase activity in patients with Type 1 and Type 2 diabetes
Angelique L W M M Rops
Nephrology Research Laboratory, Department of Nephrology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Nephrol Dial Transplant 27:2853-61. 2012
- Targeted deletion of Klotho in kidney distal tubule disrupts mineral metabolism
Clinical Research Center, Sixth Floor, Novumhuset, Karolinska University Hospital in Huddinge, Stockholm, Sweden
J Am Soc Nephrol 23:1641-51. 2012
..Taken together, renal FGF23-Klotho signaling, which is disrupted in CKD, is essential for homeostatic control of mineral metabolism...
- Macrophage activation by heparanase is mediated by TLR-2 and TLR-4 and associates with plaque progression
Department of Cardiology and Pathology, Rambam Health Care Campus, Haifa, Israel
Arterioscler Thromb Vasc Biol 33:e56-65. 2013
..Factors and mechanisms that activate macrophages in atherosclerotic plaques are incompletely understood. We examined the capacity of heparanase to activate macrophages...
- Establishment of the anti-Klotho monoclonal antibodies and detection of Klotho protein in kidneys
Tokyo Research Laboratories, Kyowa Hakko Kogyo Co Ltd, 3 6 6, Asahi machi, Machida shi, Tokyo, 194 8533, Japan
Biochem Biophys Res Commun 267:597-602. 2000
..The mAbs established in this paper will serve as useful analytical, pathological, and diagnostic tools to disclose the role of Klotho protein in the suppression of a syndrome resembling human aging...
- Soluble klotho and autosomal dominant polycystic kidney disease
Institute of Physiology and Zurich Center for Integrative Human Physiology, Zurich, Switzerland
Clin J Am Soc Nephrol 7:248-57. 2012
..This study explored potential mechanisms underlying resistance to FGF23 in ADPKD...
- Heparanase 2 interacts with heparan sulfate with high affinity and inhibits heparanase activity
Cancer and Vascular Biology Research Center, Bruce Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel
J Biol Chem 285:28010-9. 2010
..03). Hpa2 appears to restrain tumor metastasis, likely by attenuating heparanase enzymatic activity, conferring a favorable outcome of head and neck cancer patients...
- The beta-glucuronidase klotho hydrolyzes and activates the TRPV5 channel
Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, Netherlands
Science 310:490-3. 2005
..We report here that TRPV5 is stimulated by the mammalian hormone klotho. Klotho, a beta-glucuronidase, hydrolyzes extracellular sugar residues on TRPV5, entrapping the channel in the plasma membrane...
- Association of heparanase gene (HPSE) single nucleotide polymorphisms with hematological malignancies
Laboratory of Molecular Immunobiology, Department of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel
Leukemia 21:2296-303. 2007
Heparanase, endo-beta-D-glucuronidase, degrades heparan sulfate glycosaminoglycans - the principal polysaccharide of the basement membrane and extracellular matrix...
- Heparanase plays a dual role in driving hepatocyte growth factor (HGF) signaling by enhancing HGF expression and activity
Vishnu C Ramani
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294 2182, USA
J Biol Chem 286:6490-9. 2011
..This work also provides further mechanistic insight into the dynamic role of heparanase in driving aggressive tumor progression...
- Structure of the mouse klotho gene and its two transcripts encoding membrane and secreted protein
Division of Molecular Genetics, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, Japan
FEBS Lett 424:6-10. 1998
..These findings provide fundamental information for further study of the kl gene which may regulate aging in vivo...
- Mammalian heparanase: what is the message?
Department of Molecular and Developmental Genetics, VIB, Leuven, Belgium
J Cell Mol Med 11:427-52. 2007
..In that context, we also briefly discuss heparanase-2, an intriguing close homologue of heparanase-1, for which, so far, no heparan sulphate-degrading activity could be demonstrated...
- Faecal microflora and beta-glucuronidase expression are altered in an irinotecan-induced diarrhea model in rats
Andrea M Stringer
Department of Medical Oncology, Royal Adelaide Hospital, University of Adelaide, Adelaide, Australia
Cancer Biol Ther 7:1919-25. 2008
..However, the pathophysiology behind this debilitating side effect remains unclear. Irinotecan causes cholinergic and delayed onset diarrhea in patients, in which beta-glucuronidase produced by gut bacteria is thought to be involved.
- Murine mucopolysaccharidosis type VII. Characterization of a mouse with beta-glucuronidase deficiency
E H Birkenmeier
Jackson Laboratory, Bar Harbor, Maine 04609
J Clin Invest 83:1258-66. 1989
We have characterized a new mutant mouse that has virtually no beta-glucuronidase activity...
- Klotho-beta overexpression as a novel target for suppressing proliferation and fibroblast growth factor receptor-4 signaling in hepatocellular carcinoma
Department of Pharmacy, National University of Singapore, Singapore
Mol Cancer 11:14. 2012
..Here, we studied the mechanistic role of its co-receptor klotho-beta (KLB) in driving elevated FGFR4 activity in HCC progression...
- Klotho, an anti-senescence related gene, is frequently inactivated through promoter hypermethylation in colorectal cancer
Department of Gastroenterology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Tumour Biol 32:729-35. 2011
..Taken together, our results suggest that KL is inactivated through promoter hypermethylation and potentially functions as a tumor suppressor gene in CRC...
- Alteration of microRNA expression in the process of mouse brain growth
National Institute of Neuroscience, NCNP, Ogawahigashi, Kodaira, Tokyo, Japan
Gene 485:46-52. 2011
- Heparanase induces tissue factor pathway inhibitor expression and extracellular accumulation in endothelial and tumor cells
Cancer and Vascular Biology Research Center, The Bruce Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel
Thromb Haemost 99:133-41. 2008
- Vascular deconjugation of quercetin glucuronide: the flavonoid paradox revealed?
Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, Spain
Mol Nutr Food Res 55:1780-90. 2011
..We aimed to determine whether glucuronidated quercetin can deconjugate in situ and whether deconjugation leads to a biological effect...
- Modulation of the heparanase-inhibiting activity of heparin through selective desulfation, graded N-acetylation, and glycol splitting
G Ronzoni Institute for Chemical and Biochemical Research, Via G Colombo, 81, 20133 Milan, Italy
J Biol Chem 280:12103-13. 2005
Heparanase is an endo-beta-glucuronidase that cleaves heparan sulfate (HS) chains of heparan sulfate proteoglycans on cell surfaces and in the extracellular matrix (ECM)...
- The FRUITFULL MADS-box gene mediates cell differentiation during Arabidopsis fruit development
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
Development 125:1509-17. 1998
..beta-glucuronidase (GUS) reporter gene expression in the enhancer trap line is observed specifically in all cell layers of the ..
- Premature aging-like phenotype in fibroblast growth factor 23 null mice is a vitamin D-mediated process
Mohammed S Razzaque
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA
FASEB J 20:720-2. 2006
..Finally, our data support a new model of interactions among Fgf-23, vitamin D, and klotho, a gene described as being associated with premature aging process...
- The ASK1-Signalosome regulates p38 MAPK activity in response to levels of endogenous oxidative stress in the Klotho mouse models of aging
C C Hsieh
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA
Aging (Albany NY) 2:597-611. 2010
..activating ASK1-signalosomes. We conclude that the Klotho suppressor-of-aging activity is linked to the ASK1-signalsome, a physiological ROS-sensitive signaling center...
- Heparanase involvement in physiology and disease
N J Nasser
Department of Oncology, Shaare Zedek Medical Center, Jerusalem, Israel
Cell Mol Life Sci 65:1706-15. 2008
..Heparanase overexpression in a variety of malignant tumors suggests that it could be a target for anti-cancer therapy...
- SST0001, a chemically modified heparin, inhibits myeloma growth and angiogenesis via disruption of the heparanase/syndecan-1 axis
Joseph P Ritchie
Department of Pathology, Center for Metabolic Bone Disease, and Comprehensive Cancer Center, University of Alabama at Birmingham, Alabama 35294, USA
Clin Cancer Res 17:1382-93. 2011
..SST0001, a nonanticoagulant heparin with antiheparanase activity, was examined for its inhibition of myeloma tumor growth in vivo and for its mechanism of action...
- Heparanase promotes growth, angiogenesis and survival of primary breast tumors
Department of Oncology, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel
Int J Cancer 118:1609-17. 2006
..Our results emphasize the significance and clarify the involvement of heparanase in primary breast cancer progression by generating a supportive microenvironment that promotes tumor growth, angiogenesis and survival...
- Alternatively spliced Spalax heparanase inhibits extracellular matrix degradation, tumor growth, and metastasis
Nicola J Nasser
Department of Oncology, Shaare Zedek Medical Center, Jerusalem 91031, Israel
Proc Natl Acad Sci U S A 106:2253-8. 2009
- The progression of aging in klotho mutant mice can be modified by dietary phosphorus and zinc
Tsukuba Research Laboratories, Kyowa Hakko Kogyo Company Limited, Tsukuba-shi, Ibaraki 305-0841, Japan
J Nutr 131:3182-8. 2001
..05). These results indicate that dietary phosphorus and zinc modulate the phenotypes of klotho mice, and that klotho expression in the kidneys is regulated not only in klotho mutant mice, but also in wild-type mice...