Gene Symbol: TIMP4
Description: TIMP metallopeptidase inhibitor 4
Alias: TIMP-4, metalloproteinase inhibitor 4, tissue inhibitor of metalloproteinase 4, tissue inhibitor of metalloproteinases 4
Species: human
Products:     TIMP4

Top Publications

  1. Lizarraga F, Espinosa M, Maldonado V, Melendez Zajgla J. Tissue inhibitor of metalloproteinases-4 is expressed in cervical cancer patients. Anticancer Res. 2005;25:623-7 pubmed
    ..Higher TIMP-4 levels were found in advanced stage disease (p=0.016, Chi-square test). TIMP-4 is expressed de novo in cervical cancer. Higher inhibitor expression levels were found in stages II and III. ..
  2. Greene J, Wang M, Liu Y, Raymond L, Rosen C, Shi Y. Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4. J Biol Chem. 1996;271:30375-80 pubmed
    ..This unique expression pattern suggests that TIMP-4 may function in a tissue-specific fashion in extracellular matrix homeostasis. ..
  3. Radomski A, Jurasz P, Sanders E, Overall C, Bigg H, Edwards D, et al. Identification, regulation and role of tissue inhibitor of metalloproteinases-4 (TIMP-4) in human platelets. Br J Pharmacol. 2002;137:1330-8 pubmed
    ..11. Human rTIMP-4 exerted a biphasic effect on HT-1080 cells-induced aggregation. 12. Thus, TIMP-4 is the major intraplatelet MMP inhibitor and it is involved in regulation of platelet aggregation and recruitment. ..
  4. Koskivirta I, Rahkonen O, Mayranpaa M, Pakkanen S, Husheem M, Sainio A, et al. Tissue inhibitor of metalloproteinases 4 (TIMP4) is involved in inflammatory processes of human cardiovascular pathology. Histochem Cell Biol. 2006;126:335-42 pubmed
    Tissue inhibitors of matrix metalloproteinases (TIMPs) comprise a family of four members, of which TIMP4 is characterized by being primarily restricted to cardiovascular structures...
  5. Ghosh A, Murphy S, Kishore R, Vaughan D. Global gene expression profiling in PAI-1 knockout murine heart and kidney: molecular basis of cardiac-selective fibrosis. PLoS ONE. 2013;8:e63825 pubmed publisher
    ..While the levels of Ankrd1, Pi16 and Timp1 proteins were elevated during EndMT, the level of Timp4 protein was decreased...
  6. Soslow J, Xu M, Slaughter J, Crum K, Chew J, Burnette W, et al. The Role of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Duchenne Muscular Dystrophy Cardiomyopathy. J Card Fail. 2019;25:259-267 pubmed publisher
    ..007], 2170 pg/mL vs 1420 pg/mL [P < .001], and 216 pg/mL vs 140pg/mL [P = .040]); TIMP4 was lower in DMD (124 pg/mL vs 263 pg/mL; P = .046)...
  7. Aller E, Mariman E, Bouwman F, van Baak M. Genetic Predictors of ?5% Weight Loss by Multidisciplinary Advice to Severely Obese Subjects. J Nutrigenet Nutrigenomics. 2017;10:32-42 pubmed publisher
    ..The C/G-G/G genotype of PPAR? (rs1801282) and the T/C genotype of TIMP4 (rs3755724) predicted ?5% weight loss after 12 months...
  8. Vishweswaraiah S, Veerappa A, Mahesh P, Jayaraju B, Krishnarao C, Ramachandra N. Molecular interaction network and pathway studies of ADAM33 potentially relevant to asthma. Ann Allergy Asthma Immunol. 2014;113:418-24.e1 pubmed publisher
    ..The proteins identified in this study were enriched for various mechanisms that are involved in airway hyperresponsiveness, and through the interaction with ADAM33, they may have potential relevance in asthma. ..
  9. Bouwman F, Boer J, Imholz S, Wang P, Verschuren W, Dollé M, et al. Gender-specific genetic associations of polymorphisms in ACE, AKR1C2, FTO and MMP2 with weight gain over a 10-year period. Genes Nutr. 2014;9:434 pubmed publisher
    ..Weight gain, when it leads to overweight or obesity, is nowadays one of the major health problems. ACE, FTO, AKR1C2, TIMP4 and MMP2 genes have been implicated in previous studies on weight regulation...

More Information


  1. Tiede S, Wassenberg M, Christ K, Schermuly R, Seeger W, Grimminger F, et al. Biomarkers of tissue remodeling predict survival in patients with pulmonary hypertension. Int J Cardiol. 2016;223:821-826 pubmed publisher
    ..MMP2, MMP9, TIMP1, and TIMP4 were measured in plasma and their potential as biomarkers for PH was evaluated...
  2. Buerki S, Grandgirard D, Datta A, Hackenberg A, Martin F, Schmitt Mechelke T, et al. Inflammatory markers in pediatric stroke: An attempt to better understanding the pathophysiology. Eur J Paediatr Neurol. 2016;20:252-260 pubmed publisher
    ..At the time of the acute event children with AIS had significantly elevated levels of MMP-9, TIMP4, IL-6, IL-8 and CRP compared to controls (p < 0.05)...
  3. Chaturvedi P, Kalani A, Familtseva A, Kamat P, Metreveli N, Tyagi S. Cardiac tissue inhibitor of matrix metalloprotease 4 dictates cardiomyocyte contractility and differentiation of embryonic stem cells into cardiomyocytes: Road to therapy. Int J Cardiol. 2015;184:350-63 pubmed publisher
    b>TIMP4 (Tissue Inhibitors of Matrix Metalloprotease 4), goes down in failing hearts and mice lacking TIMP4 show poor regeneration capacity after myocardial infarction (MI)...
  4. Montani C, Steimberg N, Boniotti J, Biasiotto G, Zanella I, Diafera G, et al. Fibroblasts maintained in 3 dimensions show a better differentiation state and higher sensitivity to estrogens. Toxicol Appl Pharmacol. 2014;280:421-33 pubmed publisher
    ..of cell organization, homeostasis and tissue repair, metalloproteinase 2 (MMP2) and its physiological inhibitor (TIMP4) changed expression in association with the relative formation of cell aggregates...
  5. Zheng J, Guo J, Huang L, Wu Q, Yin K, Wang L, et al. Genetic diagnosis of acute aortic dissection in South China Han population using next-generation sequencing. Int J Legal Med. 2018;132:1273-1280 pubmed publisher
    ..variants, which were detected for 4 times, ACTA2 for 3 times, ABCC6 and TGFBR1 twice, and NOS3, MYLK, XYLT1, TIMP4, TGFBR2, CNTN3, and PON1 once...
  6. Cao Y, Yang Y, Wang L, Li L, Zhang J, Gao X, et al. Analyses of long non-coding RNA and mRNA profiles in right ventricle myocardium of acute right heart failure in pulmonary arterial hypertension rats. Biomed Pharmacother. 2018;106:1108-1115 pubmed publisher
    ..levels of lncRNA (TCONS_00052110, TCONS_00201718, TCONS_00094247, and TCONS_00296056) and mRNA (Cxcl-1 and Timp4) were verified through qRT-PCR, the results of which were consistent with RNA sequencing...
  7. Mishra P, Kuypers N, Singh S, Leiberh N, Chavali V, Tyagi S. Cardiac stem cell niche, MMP9, and culture and differentiation of embryonic stem cells. Methods Mol Biol. 2013;1035:153-63 pubmed publisher
    ..Here, we describe the method of ESC culture and differentiation, and the expression of MMP9 and its inhibitor, tissue inhibitor of metalloproteinase-4 (TIMP4) in differentiating ESC.
  8. Ehlken C, Grundel B, Michels D, Junker B, Stahl A, Schlunck G, et al. Increased expression of angiogenic and inflammatory proteins in the vitreous of patients with ischemic central retinal vein occlusion. PLoS ONE. 2015;10:e0126859 pubmed publisher
    ..1), IGFBP4 (1.7), IL6 (10.8), LEP (3.4), MMP3 (4.3), MMP9 (3.6), MMP10 (5.4), PPBP (CXCL7 or NAP2) (11.8), TIMP4 (3.8), and VEGFA (85.3). In CRVO patients, vitreal levels of CCL2 (4.2), HGF (23.3), IGFBP2 (1.23), MMP10 (2...
  9. Zhang Y, Wang X, Han L, Zhou Y, Sun S. Green tea polyphenol EGCG reverse cisplatin resistance of A549/DDP cell line through candidate genes demethylation. Biomed Pharmacother. 2015;69:285-90 pubmed publisher
    ..and histone deacetylase (HDAC) activity, reversal of hypermethylated status and downregulated expression of GAS1, TIMP4, ICAM1 and WISP2 gene in A549/DDP cells...
  10. Wang J, Wang Y, Han J, Li Y, Xie C, Xie L, et al. Integrated analysis of microRNA and mRNA expression profiles in the left atrium of patients with nonvalvular paroxysmal atrial fibrillation: Role of miR-146b-5p in atrial fibrosis. Heart Rhythm. 2015;12:1018-26 pubmed publisher
    ..and 624 differentially expressed mRNAs, among which only 1 miRNA-target gene pair miR-146b-5p and tissue inhibitor of metalloproteinase 4 (TIMP-4) were constructed...
  11. Singh R, Howarth F, Adeghate E, Bidasee K, Singh J, Waqar T. Type 1 diabetes mellitus induces structural changes and molecular remodelling in the rat kidney. Mol Cell Biochem. 2018;449:9-25 pubmed publisher
    ..gene expression profile of ECM key components, together with elevated levels of key mediators (MMP9, integrin 5α, TIMP4, CTGF, vimentin) and reduced expressions of Cx43 and MMP2 of the ECM...
  12. Nielsen M, Andersen T, Etzerodt A, Kragstrup T, Rasmussen T, Stengaard Pedersen K, et al. A disintegrin and metalloprotease-17 and galectin-9 are important regulators of local 4-1BB activity and disease outcome in rheumatoid arthritis. Rheumatology (Oxford). 2016;55:1871-9 pubmed publisher
    ..Gal-9 is pivotal for the function of 4-1BB and induction of TNF-?. Furthermore, high plasma levels of s4-1BB were associated with the number of swollen joints, but also with a low DAS28-CRP after 2 years treatment in early RA. ..
  13. Tofrizal A, Fujiwara K, Azuma M, Kikuchi M, Jindatip D, Yashiro T, et al. Tissue inhibitors of metalloproteinase-expressing cells in human anterior pituitary and pituitary adenoma. Med Mol Morphol. 2017;50:145-154 pubmed publisher
    ..and control pituitary were obtained during surgery, and in situ hybridization for TIMP1, TIMP2, TIMP3, and TIMP4, followed by immunohistochemistry, was used to characterize TIMP-expressing cells...
  14. Wu Y, Lee M, Ido Y, Fried S. High-fat diet-induced obesity regulates MMP3 to modulate depot- and sex-dependent adipose expansion in C57BL/6J mice. Am J Physiol Endocrinol Metab. 2017;312:E58-E71 pubmed publisher
    ..MMP3 activity also decreased (significant in ING). Timp4 mRNA was expressed mainly in adipocytes, and HFD-induced obesity tended to increase the ratio of TIMP4 to MMP3 ..
  15. Ketsawatsomkron P, Keen H, Davis D, Lu K, Stump M, De Silva T, et al. Protective Role for Tissue Inhibitor of Metalloproteinase-4, a Novel Peroxisome Proliferator-Activated Receptor-γ Target Gene, in Smooth Muscle in Deoxycorticosterone Acetate-Salt Hypertension. Hypertension. 2016;67:214-22 pubmed publisher
    ..Our findings highlight a protective mechanism induced by PPARγ in deoxycorticosterone acetate-salt treatment, establishing a novel mechanistic link between PPARγ and TIMP-4. ..
  16. Harvie M, Sims A, Pegington M, Spence K, Mitchell A, Vaughan A, et al. Intermittent energy restriction induces changes in breast gene expression and systemic metabolism. Breast Cancer Res. 2016;18:57 pubmed publisher
    ..cell differentiation (secretoglobulins, milk proteins and mucins) and decreased collagen synthesis (TNMD, PCOLCE2, TIMP4). There was no appreciable effect of IER on breast gene expression in the other nine subjects...
  17. Zhao T, Huang X, Xia Y. Human heart cell proteins interacting with a C-terminally truncated 2A protein of coxsackie B3 virus: identification by the yeast two-hybrid system. Virus Genes. 2016;52:172-8 pubmed publisher
    ..aa deletion at the C-terminus as the bait protein, four interactive cellular proteins were identified, including TIMP4, MYL2, COX7C, and ENO1. These proteins are mostly related to protein degradation and metabolism...
  18. Graubner F, Boos A, Aslan S, Kücükaslan I, Kowalewski M. Uterine and placental distribution of selected extracellular matrix (ECM) components in the dog. Reproduction. 2018;155:403-421 pubmed publisher
    ..We found that canine free-floating embryos affect gene expression of FN1, ECM1 and TIMP4 This seems to be associated with modulation of trophoblast invasion, and proliferative and adhesive functions ..
  19. Chaturvedi P, Tyagi S. Epigenetic silencing of TIMP4 in heart failure. J Cell Mol Med. 2016;20:2089-2101 pubmed publisher
    Tissue inhibitor of matrix metalloprotease 4 (TIMP4) is endogenously one of the key modulators of matrix metalloprotease 9 (MMP9) and we have reported earlier that cardiac specific TIMP4 instigates contractility and helps in ..
  20. Thakur S, Nabbi A, Klimowicz A, Riabowol K. Stromal ING1 expression induces a secretory phenotype and correlates with breast cancer patient survival. Mol Cancer. 2015;14:164 pubmed publisher
    ..by 5-8 fold, and concomitantly decreased levels of the tissue inhibitors of metalloproteases TIMP2, TIMP3 and TIMP4 by 1.5-3.3 fold, resulting in significant increases in MMP activity as determined by zymography...
  21. Lutshumba J, Liu S, Zhong Y, Hou T, Daugherty A, Lu H, et al. Deletion of BMAL1 in Smooth Muscle Cells Protects Mice From Abdominal Aortic Aneurysms. Arterioscler Thromb Vasc Biol. 2018;38:1063-1075 pubmed publisher
    ..by deoxycorticosterone acetate-salt, and deletion of BMAL1 in SMCs selectively upregulated TIMP4 (tissue inhibitor of metalloproteinase 4) and suppressed deoxycorticosterone acetate-salt-induced MMP (matrix metalloproteinase) ..
  22. Cassanta L, Rodrigues V, Violatti Filho J, Teixeira Neto B, Tavares V, Bernal E, et al. Modulation of Matrix Metalloproteinase 14, Tissue Inhibitor of Metalloproteinase 3, Tissue Inhibitor of Metalloproteinase 4, and Inducible Nitric Oxide Synthase in the Development of Periapical Lesions. J Endod. 2017;43:1122-1129 pubmed publisher
    ..However, there were no differences in the expression of MMP-19 between the 3 groups. Our data suggest that the expression of MMP-14, TIMP-3, and TIMP-4 is associated with the development of periapical lesions. ..
  23. Nguyen T, Shynlova O, Lye S. Matrix Metalloproteinase Expression in the Rat Myometrium During Pregnancy, Term Labor, and Postpartum. Biol Reprod. 2016;95:24 pubmed publisher
    ..Timp1-Timp4 were stably expressed throughout gestation with some fluctuations PP...
  24. Serralheiro P, Novais A, Cairrão E, Maia C, Costa Almeida C, Verde I. Variability of MMP/TIMP and TGF-?1 Receptors throughout the Clinical Progression of Chronic Venous Disease. Int J Mol Sci. 2017;19: pubmed publisher
    ..i>MMP2, MMP8, MMP9, MMP12, MMP13, TIMP1, TIMP2, TIMP3, TIMP4, TGF?R1, TGF?R2, and TGF?R3 gene expression analysis, and then to immunohistochemistry ..
  25. Kotnala S, Tyagi A, Muyal J. rHuKGF ameliorates protease/anti-protease imbalance in emphysematous mice. Pulm Pharmacol Ther. 2017;45:124-135 pubmed publisher
    ..due to rHuKGF supplementation the protein expressions of CRP, MMP2, MMP7, MMP8 & CTSE, SERPINE1, SERPINA1, TIMP4, GSTA1, HDAC3, PCNA, CDH1, SP-B & SP-C were ameliorated...
  26. Wetzl V, Tiede S, Faerber L, Weissmann N, Schermuly R, Ghofrani H, et al. Plasma MMP2/TIMP4 Ratio at Follow-up Assessment Predicts Disease Progression of Idiopathic Pulmonary Arterial Hypertension. Lung. 2017;195:489-496 pubmed publisher
    ..The aim of this study was to investigate MMP/TIMP ratios of selected biomarkers (MMP2, MMP9, TIMP1, TIMP4) at follow-up examination (V2) and their prognostic value in patients with idiopathic pulmonary arterial ..
  27. Chen J, Tellez G, Escobar J, Vazquez Anon M. Impact of Trace Minerals on Wound Healing of Footpad Dermatitis in Broilers. Sci Rep. 2017;7:1894 pubmed publisher
    ..LTM and/or HTM increased gene expression of VEGF, TIMP3, TIMP4, MMP13, ITGA2, ITGA3 and CD40, which promoted collagen synthesis, deposition and organization; cell migration, ..
  28. Dang L, Wang Y, Xue Y, He L, Li Y, Xiong J. Low-dose UVB irradiation prevents MMP2-induced skin hyperplasia by inhibiting inflammation and ROS. Oncol Rep. 2015;34:1478-86 pubmed publisher
    ..Further investigation of MMP2 inhibitors of TIMP2/TIMP4 showed an upregulated TIMP2 expression, but not TIMP4...
  29. Kaur N, Sunil Kumar B, Mahajan K, Singh S. Expression and characterization of tissue inhibitor of metalloproteinase 4 from complex canine mammary carcinomas. J Immunoassay Immunochem. 2016;37:515-26 pubmed publisher
    ..TIMP-4 could act as a marker of canine mammary tumors. To the best of our knowledge, this is the first report of heterologous expression of TIMP-4 from complex canine mammary carcinomas. ..
  30. Sakamuri S, Takawale A, Basu R, Fedak P, Freed D, Sergi C, et al. Differential impact of mechanical unloading on structural and nonstructural components of the extracellular matrix in advanced human heart failure. Transl Res. 2016;172:30-44 pubmed publisher
    ..Tissue inhibitor of metalloproteinase (TIMP)3 and TIMP4 messenger RNA and protein showed the greatest reduction in no-LVAD hearts...
  31. Chegini N, Rhoton Vlasak A, Williams R. Expression of matrix metalloproteinase-26 and tissue inhibitor of matrix metalloproteinase-3 and -4 in endometrium throughout the normal menstrual cycle and alteration in users of levonorgestrel implants who experience irregular uterine bleeding. Fertil Steril. 2003;80:564-70 pubmed
    ..Further elevations in MMP-26 are seen in users of levonorgestrel implants who experience irregular uterine bleeding. These substances thus seem to play a role in hormonal regulation and endometrial tissue remodeling. ..
  32. Zhang Y, Ma Q, Yang H, Long Y, Liu X, Zhou C. Maternal plasma TIMP-4 levels combined with clinical risk factors for the early prediction of pregnancy-induced hypertension. Arch Gynecol Obstet. 2015;292:1043-50 pubmed publisher
    ..Future multicenter studies including greater numbers of samples, analyzed proteins, and risk factors are needed to obtain a higher predictive value of the model for the clinical diagnosis of PIH. ..
  33. Gershtein E, Korotkova E, Shcherbakov A, Prorokov V, Golovkov D, Kushlinskii N. Matrix metalloproteinases 7 and 9 and their types 1 and 4 tissue inhibitors in tumors and plasma of patients with colorectal cancer. Bull Exp Biol Med. 2007;143:459-62 pubmed
    ..Plasma concentrations of the studied proteins did not correlate with their levels in the tumor, did not surpass the normal, and did not decease after removal of the primary tumor in the majority of patients. ..
  34. Kai H, Butler G, Morrison C, King A, Pelman G, Overall C. Utilization of a novel recombinant myoglobin fusion protein expression system to characterize the tissue inhibitor of metalloproteinase (TIMP)-4 and TIMP-2 C-terminal domain and tails by mutagenesis. The importance of acidic residues in binding the M. J Biol Chem. 2002;277:48696-707 pubmed
  35. Chen C, Chen P, Huang H, Lin Y, Fang H. Overexpression of matrix metalloproteinases in lung tissue of patients with primary spontaneous pneumothorax. Respiration. 2014;88:418-25 pubmed publisher
    ..MMP-2, MMP-9, MMP-7 and TIMP-2 were upregulated in PSP lesions. These results suggest that an imbalance between the expression of proteases and antiproteases may be involved in the pathogeneses of PSP. ..
  36. Ban J, Yoon K, Kim S, Kang S, Chung J. Promoter polymorphism (rs3755724, -55C/T) of tissue inhibitor of metalloproteinase 4 (TIMP4) as a risk factor for Kawasaki disease with coronary artery lesions in a Korean population. Pediatr Cardiol. 2009;30:331-5 pubmed publisher
    ..Tissue inhibitors of matrix metalloproteinases (TIMPs) comprise a family of four members, of which TIMP4 is characterized by its restriction to cardiovascular structures...
  37. Elias G, Ioannis M, Theodora P, Dimitrios P, Despoina P, Kostantinos V, et al. Circulating tissue inhibitor of matrix metalloproteinase-4 (TIMP-4) in systemic sclerosis patients with elevated pulmonary arterial pressure. Mediators Inflamm. 2008;2008:164134 pubmed publisher
    ..03), independently of age, extent of skin sclerosis, or lung fibrosis, suggesting a cardiopulmonary vasculature-specific role of TIMP-4 activation in SSc. ..
  38. Del Porto F, Cifani N, Proietta M, Toni D, Taurino M. MMP-12 and TIMP Behavior in Symptomatic and Asymptomatic Critical Carotid Artery Stenosis. J Stroke Cerebrovasc Dis. 2017;26:334-338 pubmed publisher
    ..Moreover, we suggest that a specific pattern of matrix degrading enzyme inhibitors arises during the early phases of stroke. ..
  39. Kapsoritakis A, Kapsoritaki A, Davidi I, Lotis V, Manolakis A, Mylonis P, et al. Imbalance of tissue inhibitors of metalloproteinases (TIMP) - 1 and - 4 serum levels, in patients with inflammatory bowel disease. BMC Gastroenterol. 2008;8:55 pubmed publisher
    ..Gender tends to influence TIMP-1 and TIMP-4 serum levels. These new findings bring into question the potential role of TIMPs in IBD, thus underlining the need for future studies which could offer new insight into this matter. ..
  40. Liss M, Sreedhar N, Keshgegian A, Sauter G, Chernick M, Prendergast G, et al. Tissue inhibitor of metalloproteinase-4 is elevated in early-stage breast cancers with accelerated progression and poor clinical course. Am J Pathol. 2009;175:940-6 pubmed publisher
    ..Our findings prompt further evaluation of TIMP-4 as a simple prognostic marker that may help identify patients with early-stage breast cancer who could benefit from more aggressive treatment at diagnosis. ..
  41. Haerian B, Sha ari H, Fong C, Tan H, Wong S, Ong L, et al. Contribution of TIMP4 rs3755724 polymorphism to susceptibility to focal epilepsy in Malaysian Chinese. J Neuroimmunol. 2015;278:137-43 pubmed publisher
    ..b>Tissue inhibitor of metalloproteinase 4 (TIMP4) is an inflammation-induced apoptosis and matrix turnover factor involved in several ..
  42. Pohar N, Godenschwege T, Buchner E. Invertebrate tissue inhibitor of metalloproteinase: structure and nested gene organization within the synapsin locus is conserved from Drosophila to human. Genomics. 1999;57:293-6 pubmed
    ..We therefore speculate that the human TIMP4 gene will be located in intron V of the human synapsin-II gene on chromosome 3p25, and we present preliminary ..
  43. Donnini S, Monti M, Roncone R, Morbidelli L, Rocchigiani M, Oliviero S, et al. Peroxynitrite inactivates human-tissue inhibitor of metalloproteinase-4. FEBS Lett. 2008;582:1135-40 pubmed publisher
    ..HPLC/ESI-MS/MS analysis of peroxynitrite-treated TIMP-4 showed modifications at Y114, Y195, Y188 and Y190. In conclusion, TIMP-4 nitration might be a potential mechanism contributing to cardiovascular disease and cancer. ..
  44. Sakamuri S, Watts R, Takawale A, Wang X, Hernández Anzaldo S, Bahitham W, et al. Absence of Tissue Inhibitor of Metalloproteinase-4 (TIMP4) ameliorates high fat diet-induced obesity in mice due to defective lipid absorption. Sci Rep. 2017;7:6210 pubmed publisher
    ..b>TIMP4 is highly expressed in adipose tissue, its levels are further elevated following high-fat diet, but its role in ..
  45. Meschiari C, Jung M, Iyer R, Yabluchanskiy A, Toba H, Garrett M, et al. Macrophage overexpression of matrix metalloproteinase-9 in aged mice improves diastolic physiology and cardiac wound healing following myocardial infarction. Am J Physiol Heart Circ Physiol. 2017;:ajpheart.00453.2017 pubmed publisher
    ..subunit A (Pdgfa), and transforming growth factor beta 3 (Tgfb3) along with elevated tissue inhibitor of MMP-4 (Timp4) macrophage expression reveal mechanisms of indirect downstream effects on fibroblasts and neovascularization...
  46. Zavadzkas J, Stroud R, Bouges S, Mukherjee R, Jones J, Patel R, et al. Targeted overexpression of tissue inhibitor of matrix metalloproteinase-4 modifies post-myocardial infarction remodeling in mice. Circ Res. 2014;114:1435-45 pubmed publisher
    ..plaque forming units/mL) encoding green fluorescent protein (GFP) and the full-length human TIMP-4 (Ad-GFP-TIMP4) or GFP...
  47. Pilka R, Noskova V, Domanski H, Andersson C, Hansson S, Casslen B. Endometrial TIMP-4 mRNA is expressed in the stroma, while TIMP-4 protein accumulates in the epithelium and is released to the uterine fluid. Mol Hum Reprod. 2006;12:497-503 pubmed
    ..MMP-26 is stored in epithelial cells in its active form, is not released spontaneously and is controlled by TIMP-4 in both stroma and uterine fluid. ..
  48. Chen Q, Lu L, Peng W, Hu J, Yan X, Wang L, et al. Polymorphisms of MMP-3 and TIMP-4 genes affect angiographic coronary plaque progression in non-diabetic and type 2 diabetic patients. Clin Chim Acta. 2009;405:97-103 pubmed publisher
    ..This study demonstrated that MMP-3 and TIMP-4 polymorphisms affect angiographic coronary PP in type 2 diabetic and non-diabetic patients. ..
  49. Bigg H, Shi Y, Liu Y, Steffensen B, Overall C. Specific, high affinity binding of tissue inhibitor of metalloproteinases-4 (TIMP-4) to the COOH-terminal hemopexin-like domain of human gelatinase A. TIMP-4 binds progelatinase A and the COOH-terminal domain in a similar manner to TIMP-2. J Biol Chem. 1997;272:15496-500 pubmed
    ..This new phenomenon may be of important physiological significance in modulating the cell surface activation of progelatinase A. ..
  50. Martinez E, Lilyanna S, Wang P, Vardy L, Jiang X, Armugam A, et al. MicroRNA-31 promotes adverse cardiac remodeling and dysfunction in ischemic heart disease. J Mol Cell Cardiol. 2017;112:27-39 pubmed publisher
    ..cardiac troponin-T (Tnnt2), E2F transcription factor 6 (E2f6), mineralocorticoid receptor (Nr3c2) and metalloproteinase inhibitor 4 (Timp4) mRNAs...
  51. Drewlo S, Czikk M, Baczyk D, Lye S, Kingdom J. Glial cell missing-1 mediates over-expression of tissue inhibitor of metalloproteinase-4 in severe pre-eclamptic placental villi. Hum Reprod. 2011;26:1025-34 pubmed publisher
    ..5-fold, n = 12) and protein level (9.8-fold) of tissue inhibitor of metalloproteinase-4 (TIMP4) following repression of GCM1 (70 ± 7%) by small interfering-RNA, using RT-PCR and western blot, respectively...
  52. Lee S, Desai K, Iczkowski K, Newcomer R, Wu K, Zhao Y, et al. Coordinated peak expression of MMP-26 and TIMP-4 in preinvasive human prostate tumor. Cell Res. 2006;16:750-8 pubmed
    ..The present study indicates that MMP-26 and TIMP-4 may play an integral role during the conversion of HGPIN to invasive cancer and may also serve as markers for early prostate cancer diagnosis. ..
  53. Nour N, Mayer G, Mort J, Salvas A, Mbikay M, Morrison C, et al. The cysteine-rich domain of the secreted proprotein convertases PC5A and PACE4 functions as a cell surface anchor and interacts with tissue inhibitors of metalloproteinases. Mol Biol Cell. 2005;16:5215-26 pubmed
    ..In conclusion, the CRD of PC5A and PACE4 functions as a cell surface anchor favoring the processing of their cognate surface-anchored substrates, including endothelial lipase. ..
  54. Zhang J, Cao Y, Zhao Y, Sang Q, Duan E. Expression of matrix metalloproteinase-26 and tissue inhibitor of metalloproteinase-4 in human normal cytotrophoblast cells and a choriocarcinoma cell line, JEG-3. Mol Hum Reprod. 2002;8:659-66 pubmed
  55. Pilka R, Domanski H, Hansson S, Eriksson P, Casslen B. Endometrial TIMP-4 mRNA is high at midcycle and in hyperplasia, but down-regulated in malignant tumours. Coordinated expression with MMP-26. Mol Hum Reprod. 2004;10:641-50 pubmed
    ..Similarities in the cyclic patterns of TIMP-4 mRNA and MMP-26 mRNA, together with the fact that TIMP-4 is a potent inhibitor of MMP-26, suggest a functional relationship, and furthermore a role in human implantation. ..
  56. Rorive S, Lopez X, Maris C, Trepant A, Sauvage S, Sadeghi N, et al. TIMP-4 and CD63: new prognostic biomarkers in human astrocytomas. Mod Pathol. 2010;23:1418-28 pubmed publisher
    ..It identifies TIMP-4 and CD63 as markers of the astrocytic phenotype in patients with gliomas. In addition, this work highlights the contribution of high TIMP-4/CD63 co-expression to the adverse outcomes of patients with glioblastomas. ..
  57. Tsai H, Hsieh M, Chiou H, Lee H, Hsin M, Liou Y, et al. TIMP-3 -1296 T>C and TIMP-4 -55 T>C gene polymorphisms play a role in the susceptibility of hepatocellular carcinoma among women. Tumour Biol. 2014;35:8999-9007 pubmed publisher
    ..In conclusion, gene polymorphisms of TIMP-3 -1296 T>C (rs9619311) and TIMP-4 -55 T>C (rs3755724) play a role in the susceptibility of HCC among Taiwan women. ..
  58. Janiak M, Paskal W, Rak B, Garbicz F, Jarema R, Sikora K, et al. TIMP4 expression is regulated by miR-200b-3p in prostate cancer cells. APMIS. 2017;125:101-105 pubmed publisher
    In prostate cancer TIMP4 expression level fluctuates with tumor progression. The mechanism and factors influencing its expression remain unclear. The aim of the study was to test the hypothesis on regulation of TIMP4 by microRNA-200b-3p...
  59. Kuliczkowski W, Radomski M, GÄ…sior M, Urbaniak J, Kaczmarski J, Mysiak A, et al. MMP-2, MMP-9, and TIMP-4 and Response to Aspirin in Diabetic and Nondiabetic Patients with Stable Coronary Artery Disease: A Pilot Study. Biomed Res Int. 2017;2017:9352015 pubmed publisher
    ..TIMP-4 may serve as a marker of TXA2-mediated platelet aggregation. Chronically elevated plasma glucose increases plasma MMP-2, and HPR potentiates this phenomenon. ..
  60. Wojciechowski R, Bailey Wilson J, Stambolian D. Association of matrix metalloproteinase gene polymorphisms with refractive error in Amish and Ashkenazi families. Invest Ophthalmol Vis Sci. 2010;51:4989-95 pubmed publisher
    ..The results suggest that the MMP1 and MMP2 genes are involved in refractive variation in the AMISH. Genetic and/or environmental heterogeneity most likely contribute to differences in association results between ethnic groups. ..
  61. Lizarraga F, Ceballos Cancino G, Espinosa M, Vazquez Santillan K, Maldonado V, Melendez Zajgla J. Tissue Inhibitor of Metalloproteinase-4 Triggers Apoptosis in Cervical Cancer Cells. PLoS ONE. 2015;10:e0135929 pubmed publisher
    ..This report shows that TIMP-4 regulates carcinogenesis through apoptosis activation in cervical cancer cells. Understanding TIMP-4 effects in tumorigenesis may provide clues for future therapies. ..
  62. Zhao Y, Xiao A, Park H, Newcomer R, Yan M, Man Y, et al. Endometase/matrilysin-2 in human breast ductal carcinoma in situ and its inhibition by tissue inhibitors of metalloproteinases-2 and -4: a putative role in the initiation of breast cancer invasion. Cancer Res. 2004;64:590-8 pubmed
    ..Higher levels of MMP-26 mRNA were also detected in DCIS cells by in situ hybridization...
  63. Yim S, Kim S, Park H, Jeon H, Jo B, Kang W, et al. Assessment of the correlation between TIMP4 SNPs and schizophrenia and autism spectrum disorders. Mol Med Rep. 2013;7:489-94 pubmed publisher
    ..To investigate whether TIMP4 polymorphisms are associated with schizophrenia and autism spectrum disorders (ASDs), 480 patients (schizophrenia, ..
  64. Azhikina T, Kozlova A, Skvortsov T, Sverdlov E. Heterogeneity and degree of TIMP4, GATA4, SOX18, and EGFL7 gene promoter methylation in non-small cell lung cancer and surrounding tissues. Cancer Genet. 2011;204:492-500 pubmed publisher
    ..high resolution melting analysis to assess methylation of CpG islands within the promoters of the TIMP4, GATA4, SOX18, and EGFL7 genes in samples of non-small cell lung cancer and surrounding apparently normal tissue ..
  65. Wakula P, Neumann B, Kienemund J, Thon Gutschi E, Stojakovic T, Manninger M, et al. CHA2DS2-VASc score and blood biomarkers to identify patients with atrial high-rate episodes and paroxysmal atrial fibrillation. Europace. 2017;19:544-551 pubmed publisher
    ..TIMP-4, NT-proANP, NT-proBNP were strongest associated with PAF and AHRE. The discriminatory performance of CHADS2-VASc for PAF was increased by addition of selected biomarkers. ..
  66. Hernandez Barrantes S, Shimura Y, Soloway P, Sang Q, Fridman R. Differential roles of TIMP-4 and TIMP-2 in pro-MMP-2 activation by MT1-MMP. Biochem Biophys Res Commun. 2001;281:126-30 pubmed
    ..A balance between TIMP-2 and TIMP-4 may be a critical factor in determining the degradative potential of cells in normal and pathological conditions. ..
  67. Lee H, Lee G, Nah S, Lee K, Yang H, Kim Y, et al. Association of TIMP-4 gene polymorphism with the risk of osteoarthritis in the Korean population. Rheumatol Int. 2008;28:845-50 pubmed publisher
    ..We demonstrated that the C/T polymorphism which is located on the 3'-untranslational regions of the TIMP-4 gene might be associated with susceptibility to OA patients. ..
  68. Sun Y, Huang Z, Wang Z, Li C, Meng X, Zhang Y, et al. TGF-β1 and TIMP-4 regulate atrial fibrosis in atrial fibrillation secondary to rheumatic heart disease. Mol Cell Biochem. 2015;406:131-8 pubmed publisher
    To investigate the involvement of transforming growth factor-β1 (TGF-β1) and tissue inhibitor of metalloproteinase 4 (TIMP-4) in influencing the severity of atrial fibrosis in rheumatic heart disease (RHD) patients with atrial ..
  69. Olson T, Hirohata S, Ye J, Leco K, Seldin M, Apte S. Cloning of the human tissue inhibitor of metalloproteinase-4 gene (TIMP4) and localization of the TIMP4 and Timp4 genes to human chromosome 3p25 and mouse chromosome 6, respectively. Genomics. 1998;51:148-51 pubmed
    We have isolated genomic DNA containing the human tissue inhibitor of metalloproteinases-4 gene (TIMP4) and determined the structure of the exons comprising the gene...
  70. Boufraqech M, Zhang L, Nilubol N, Sadowski S, Kotian S, Quezado M, et al. Lysyl Oxidase (LOX) Transcriptionally Regulates SNAI2 Expression and TIMP4 Secretion in Human Cancers. Clin Cancer Res. 2016;22:4491-504 pubmed publisher
    ..patients with metastatic, breast and colon cancer, and tissue array for thyroid cancer were assessed for SNAI2 and TIMP4 expression by immunohistochemistry. We found that LOX knockdown decreases SNAI2 expression in cancer cell lines...
  71. Wei Y, Cui C, Lainscak M, Zhang X, Li J, Huang J, et al. Type-specific dysregulation of matrix metalloproteinases and their tissue inhibitors in end-stage heart failure patients: relationship between MMP-10 and LV remodelling. J Cell Mol Med. 2011;15:773-82 pubmed publisher
    ..Our findings suggest that type-specific dysregulation of MMPs and TIMPs is associated with LV remodelling in end-stage HF patients, and MMP-10 may act as a novel biomarker for LV remodelling. ..
  72. Lizarraga F, Espinosa M, Ceballos Cancino G, Vazquez Santillan K, Bahena Ocampo I, Schwarz Cruz Y Celis A, et al. Tissue inhibitor of metalloproteinases-4 (TIMP-4) regulates stemness in cervical cancer cells. Mol Carcinog. 2016;55:1952-1961 pubmed publisher
    ..Understanding TIMP-4 effects on tumorigenesis may provide clues for future therapies design. © 2015 Wiley Periodicals, Inc. ..
  73. Zhao Y, Zhou X, Liao X, Yang Z. [Expression and significance of matrix metalloproteinase-1,9, tissue inhibitor of metalloproteinase-4 and extracellular matrix metalloproteinase inducer in the myocardium of congestive heart failure in patients with rheumatic heart diseases]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2009;34:790-5 pubmed
    ..MMPs, TIMP, and EMMPRIN were significantly unbalanced in the myocardium of congestive heart failure patients with rheumatic heart diseases. They may play an important role in congestive heart failure through myocardial remodeling. ..
  74. Troeberg L, Tanaka M, Wait R, Shi Y, Brew K, Nagase H. E. coli expression of TIMP-4 and comparative kinetic studies with TIMP-1 and TIMP-2: insights into the interactions of TIMPs and matrix metalloproteinase 2 (gelatinase A). Biochemistry. 2002;41:15025-35 pubmed
    ..Similar models of interaction may apply to TIMP-4. The latter low-affinity site functions in conjunction with the active site of MMP-2 to generate a tight enzyme-inhibitor complex. ..
  75. Lee E, Shen Q, Pitts R, Guo M, Wu M, Sun S, et al. Serum metalloproteinases MMP-2, MMP-9, and metalloproteinase tissue inhibitors in patients are associated with arteriovenous fistula maturation. J Vasc Surg. 2011;54:454-9; discussion 459-60 pubmed publisher
    ..Further follow-up studies to determine the predictability of AVF maturation using relative patient serum levels of MMP-2 and TIMP-2 should be performed. ..
  76. Huang W, Li W, Dehnade F, Zafarullah M. Tissue inhibitor of metalloproteinases-4 (TIMP-4) gene expression is increased in human osteoarthritic femoral head cartilage. J Cell Biochem. 2002;85:295-303 pubmed
    ..Increased TIMP levels in arthritic cartilage may not be a sufficiently effective defense against cartilage resorption by excessive multiple MMPs and aggrecanases. ..
  77. Ashworth Briggs E, Toh T, Eri R, Hewitt A, Cook A. TIMP1, TIMP2, and TIMP4 are increased in aqueous humor from primary open angle glaucoma patients. Mol Vis. 2015;21:1162-72 pubmed
    ..Concentrations of TIMP1 (p = 0.0008), TIMP2 (p = 0.002), TIMP4 (p = 0.002), and MMP2 (p = 0...
  78. Weir R, Clements S, Steedman T, Dargie H, McMurray J, Squire I, et al. Plasma TIMP-4 predicts left ventricular remodeling after acute myocardial infarction. J Card Fail. 2011;17:465-71 pubmed publisher
    ..Further study of the role of the TIMPs in the pathophysiology of postinfarction remodeling is warranted. ..
  79. Song G, Yan J, Zhang Q, Li G, Chen Z. Association of tissue inhibitor of metalloproteinase gene polymorphisms and unexplained recurrent spontaneous abortions in Han Chinese couples. Eur J Obstet Gynecol Reprod Biol. 2014;181:84-8 pubmed publisher
    ..No evidence was found for any associations between the TIMP-1,-2,-3, or -4 genes SNPs with URSA in this Han Chinese Han. ..
  80. Lee M, Rapti M, Murphy G. Total conversion of tissue inhibitor of metalloproteinase (TIMP) for specific metalloproteinase targeting: fine-tuning TIMP-4 for optimal inhibition of tumor necrosis factor-{alpha}-converting enzyme. J Biol Chem. 2005;280:15967-75 pubmed
    ..Drawing together our previous experience in TACE-targeted mutagenesis by using TIMP-1 and -2 scaffolds, we have finally resolved the mystery of the selective sensitivity of TACE to TIMP-3. ..