HAS3

Summary

Gene Symbol: HAS3
Description: hyaluronan synthase 3
Alias: hyaluronan synthase 3, HA synthase 3, hyaluronate synthase 3, hyaluronic acid synthase 3
Species: human
Products:     HAS3

Top Publications

  1. Liu N, Gao F, Han Z, Xu X, Underhill C, Zhang L. Hyaluronan synthase 3 overexpression promotes the growth of TSU prostate cancer cells. Cancer Res. 2001;61:5207-14 pubmed
    b>Hyaluronan synthase 3 (HAS3) is responsible for the production of both secreted and cell-associated forms of hyaluronan and is the most active of the three isoforms of this enzyme in adults...
  2. Rilla K, Oikari S, Jokela T, Hyttinen J, Kärnä R, Tammi R, et al. Hyaluronan synthase 1 (HAS1) requires higher cellular UDP-GlcNAc concentration than HAS2 and HAS3. J Biol Chem. 2013;288:5973-83 pubmed publisher
    ..HAS1 was almost unable to secrete hyaluronan or form a hyaluronan coat, in contrast to HAS2 and HAS3. This failure of HAS1 to synthesize hyaluronan was compensated by increasing the cellular content of UDP-N-acetyl ..
  3. Spicer A, Olson J, McDonald J. Molecular cloning and characterization of a cDNA encoding the third putative mammalian hyaluronan synthase. J Biol Chem. 1997;272:8957-61 pubmed
    We report the isolation of a cDNA encoding the third putative hyaluronan synthase, HAS3. Partial cDNAs and genomic fragments of mouse Has3 were obtained using a degenerate polymerase chain reaction approach...
  4. Karousou E, Kamiryo M, Skandalis S, Ruusala A, Asteriou T, Passi A, et al. The activity of hyaluronan synthase 2 is regulated by dimerization and ubiquitination. J Biol Chem. 2010;285:23647-54 pubmed publisher
    ..COS-1 cells followed by immunoprecipitation and immunoblotting revealed homodimers; after co-transfection with Flag-HAS3, also heterodimers were seen. Furthermore, the expressed HAS2 was ubiquitinated...
  5. Nykopp T, Rilla K, Sironen R, Tammi M, Tammi R, Hamalainen K, et al. Expression of hyaluronan synthases (HAS1-3) and hyaluronidases (HYAL1-2) in serous ovarian carcinomas: inverse correlation between HYAL1 and hyaluronan content. BMC Cancer. 2009;9:143 pubmed publisher
    ..contributors to the accumulation of hyaluronan, we examined the expression of hyaluronan synthases (HAS1, HAS2 and HAS3) and hyaluronidases (HYAL1 and HYAL2), correlated with hyaluronidase enzyme activity hyaluronan content and HAS1-3 ..
  6. Takabe P, Kärnä R, Rauhala L, Tammi M, Tammi R, Pasonen Seppänen S. Melanocyte hyaluronan coat fragmentation enhances the UVB-induced TLR-4 receptor signaling and expression of proinflammatory mediators IL-6, IL-8, CXCL-1 and CXCL-10 via NF-κB activation. J Invest Dermatol. 2019;: pubmed publisher
    ..A single dose of UVB suppressed hyaluronan secretion and the expression of hyaluronan synthases HAS2, HAS3, the hyaluronan receptor CD44 and the hyaluronidase HYAL2, as well as induced the expression of inflammatory ..
  7. Sukowati C, Anfuso B, Fiore E, Ie S, Raseni A, Vascotto F, et al. Hyaluronic acid inhibition by 4-methylumbelliferone reduces the expression of cancer stem cells markers during hepatocarcinogenesis. Sci Rep. 2019;9:4026 pubmed publisher
    ..We observed that 4MU treatments in animal model down-regulated the mRNA expressions of HA-related genes Has3 and Hyal2 only in HBV-TG but not in normal WT...
  8. Melero Fernandez de Mera R, Arasu U, Kärnä R, Oikari S, Rilla K, Vigetti D, et al. Effects of mutations in the post-translational modification sites on the trafficking of hyaluronan synthase 2 (HAS2). Matrix Biol. 2018;: pubmed publisher
    ..increased HA secretion by HAS2, likely by inhibiting endocytosis of the enzyme from PM, as reported before for HAS3. Green-to-red photo-conversion of Dendra2-HAS2 constructs suggested slower decay of K190R and S221A than HAS2 wt, ..
  9. Reeves S, Kang I, Chan C, Barrow K, Kolstad T, White M, et al. Asthmatic bronchial epithelial cells promote the establishment of a Hyaluronan-enriched, leukocyte-adhesive extracellular matrix by lung fibroblasts. Respir Res. 2018;19:146 pubmed publisher
    ..We observed increased expression of HA synthases HAS2 and HAS3 in HLFs co-cultured with asthmatic BECs...

More Information

Publications82

  1. Fujimoto K, Hasebe T, Kajita M, Ishizuya Oka A. Expression of hyaluronan synthases upregulated by thyroid hormone is involved in intestinal stem cell development during Xenopus laevis metamorphosis. Dev Genes Evol. 2018;228:267-273 pubmed publisher
    ..Our quantitative RT-PCR analysis indicated that the mRNA expression of HAS2 and HAS3, but not that of HAS1 and HAS-rs, a unique Xenopus HAS-related sequence, is upregulated concomitantly with the ..
  2. Nishiyama K, Maruyama R, Niinuma T, Kai M, Kitajima H, Toyota M, et al. Screening for long noncoding RNAs associated with oral squamous cell carcinoma reveals the potentially oncogenic actions of DLEU1. Cell Death Dis. 2018;9:826 pubmed publisher
    ..that DLEU1 knockdown significantly affects expression of a number of cancer-related genes in OSCC cells, including HAS3, CD44, and TP63, suggesting that DLEU1 regulates HA-CD44 signaling...
  3. Wu R, Sedlmeier G, Kyjacova L, Schmaus A, Philipp J, Thiele W, et al. Hyaluronic acid-CD44 interactions promote BMP4/7-dependent Id1/3 expression in melanoma cells. Sci Rep. 2018;8:14913 pubmed publisher
    ..Importantly, we found that coordinate expression of Id1 or Id3 with HA synthases HAS2, HAS3, and CD44 is associated with reduced overall survival of cutaneous melanoma patients...
  4. Tateya I, Tateya T, Watanuki M, Bless D. Homeostasis of hyaluronic acid in normal and scarred vocal folds. J Voice. 2015;29:133-9 pubmed publisher
    ..At 2 months, Has3 and Hyal3 mRNA showed higher expressions than normal...
  5. Bart G, Vico N, Hassinen A, Pujol F, Deen A, Ruusala A, et al. Fluorescence resonance energy transfer (FRET) and proximity ligation assays reveal functionally relevant homo- and heteromeric complexes among hyaluronan synthases HAS1, HAS2, and HAS3. J Biol Chem. 2015;290:11479-90 pubmed publisher
    ..It has been shown that HAS2 immunoprecipitates contain functional HAS2 homomers and also heteromers with HAS3 (Karousou, E., Kamiryo, M., Skandalis, S. S., Ruusala, A., Asteriou, T., Passi, A., Yamashita, H., Hellman, U...
  6. Cheng A, Yin H, Chen A, Liu Y, Chuang M, He H, et al. Celecoxib and Pioglitazone as Potential Therapeutics for Regulating TGF-?-Induced Hyaluronan in Dysthyroid Myopathy. Invest Ophthalmol Vis Sci. 2016;57:1951-9 pubmed publisher
    ..Tumor necrosis factor ?-induced TGF-? in turn significantly increased HA expression and HAS3 level, but not HAS1 and HAS2...
  7. Rauhala L, Jokela T, Kärnä R, Bart G, Takabe P, Oikari S, et al. Extracellular ATP activates hyaluronan synthase 2 (HAS2) in epidermal keratinocytes via P2Y2, Ca2+ signaling, and MAPK pathways. Biochem J. 2018;475:1755-1772 pubmed publisher
    ..Smaller but more persistent up-regulation of HAS3 and CD44, and delayed up-regulation of HAS1 were also observed...
  8. Bai F, Jiu M, You Y, Feng Y, Xin R, Liu X, et al. miR?29a?3p represses proliferation and metastasis of gastric cancer cells via attenuating HAS3 levels. Mol Med Rep. 2018;17:8145-8152 pubmed publisher
    ..In addition, it was revealed that miR?29a?3p functioned through downregulating hyaluronan synthase 3 expression...
  9. Chavoshinejad R, Marei W, Hartshorne G, Fouladi Nashta A. Localisation and endocrine control of hyaluronan synthase (HAS) 2, HAS3 and CD44 expression in sheep granulosa cells. Reprod Fertil Dev. 2016;28:765-75 pubmed publisher
    ..Accordingly, the expression of HAS2, HAS3 and CD44 mRNA was measured in cultured granulosa cells exposed to 0-50ngmL(-1) of 17β-oestradiol and different ..
  10. Wang Y, Lauer M, Anand S, Mack J, Maytin E. Hyaluronan synthase 2 protects skin fibroblasts against apoptosis induced by environmental stress. J Biol Chem. 2014;289:32253-65 pubmed publisher
    ..We previously reported that Has1 and Has3 double knock-out (Has1/3 null) mice show accelerated wound closure and increased numbers of fibroblasts in the ..
  11. Gatti V, Fierro C, Compagnone M, Giangrazi F, Markert E, Bongiorno Borbone L, et al. ΔNp63 regulates the expression of hyaluronic acid-related genes in breast cancer cells. Oncogenesis. 2018;7:65 pubmed publisher
    ..At molecular level, we found that ΔNp63 regulates the expression of HA-related genes, such as the HA synthase HAS3, the hyaluronidase HYAL-1 and CD44, the major HA cell membrane receptor...
  12. Katona E, Juhasz T, Somogyi C, Hajdú T, Szász C, Rácz K, et al. PP2B and ERK1/2 regulate hyaluronan synthesis of HT168 and WM35 human melanoma cell lines. Int J Oncol. 2016;48:983-97 pubmed publisher
    ..HAS2 and HAS3 were detected in all the samples, while the expression of HAS1 was not detectable in any case...
  13. di Martino E, Kelly G, Roulson J, Knowles M. Alteration of cell-cell and cell-matrix adhesion in urothelial cells: an oncogenic mechanism for mutant FGFR3. Mol Cancer Res. 2015;13:138-48 pubmed publisher
    ..FGFR3 in bladder cancer cells induced converse changes in transcript levels of CDH16, PLAU, MMP10, EPCAM, TNC, and HAS3, confirming them as downstream gene targets of mutant FGFR3...
  14. Kiene L, Homann S, Suvorava T, Rabausch B, Müller J, Kojda G, et al. Deletion of Hyaluronan Synthase 3 Inhibits Neointimal Hyperplasia in Mice. Arterioscler Thromb Vasc Biol. 2016;36:e9-16 pubmed publisher
    ..HA is synthesized by 3 different HA synthases (HAS1, HAS2, and HAS3). Aim of this study was to unravel the role of the HAS3 isoenzyme during experimental neointimal hyperplasia...
  15. Masarwah A, Tammi M, Sudah M, Sutela A, Oikari S, Kosma V, et al. The reciprocal association between mammographic breast density, hyaluronan synthesis and patient outcome. Breast Cancer Res Treat. 2015;153:625-34 pubmed publisher
    ..VLD showed an increased level of HA-positive carcinoma cells and stromal HA, HAS2, and HAS3. Tumors presenting as masses had more HA-positive carcinoma cells and more stromal HAS2 and HAS3...
  16. Mohey Elsaeed O, Marei W, Fouladi Nashta A, El Saba A. Histochemical structure and immunolocalisation of the hyaluronan system in the dromedary oviduct. Reprod Fertil Dev. 2016;28:936-947 pubmed publisher
    ..the dromedary (Camelus dromedarius), focusing on the immnolocalisation of hyaluronic acid (HA) synthases (HAS2 and HAS3), hyaluronidases (HYAL2 and HYAL1) and the HA receptor CD44 in the ampulla and isthmus...
  17. Kohi S, Sato N, Cheng X, Koga A, Higure A, Hirata K. A novel epigenetic mechanism regulating hyaluronan production in pancreatic cancer cells. Clin Exp Metastasis. 2016;33:225-30 pubmed publisher
    ..This enhanced HA production by 5-aza-dC treatment was accompanied by increased mRNA expression of HAS2 and HAS3. Furthermore, increased HA production and HAS2/HAS3 mRNA expression was also observed in PDAC cells by knockdown of ..
  18. Marei W, Raheem K, Salavati M, Tremaine T, Khalid M, Fouladi Nashta A. Hyaluronan and hyaluronidase, which is better for embryo development?. Theriogenology. 2016;86:940-948 pubmed publisher
    ..In contrast, we show evidence that breakdown of HA into smaller fragments is required to maximize embryo development and blastocyst quality. ..
  19. Koistinen V, Jokela T, Oikari S, Kärnä R, Tammi M, Rilla K. Hyaluronan-positive plasma membrane protrusions exist on mesothelial cells in vivo. Histochem Cell Biol. 2016;145:531-44 pubmed publisher
    Previous observations of our research group showed that HAS2 and HAS3 overexpression in cultured cells induces the formation of long and numerous microvillus-like cell protrusions, which are present also in cultured cell types with ..
  20. Heffler M, Golubovskaya V, Conroy J, Liu S, Wang D, Cance W, et al. FAK and HAS inhibition synergistically decrease colon cancer cell viability and affect expression of critical genes. Anticancer Agents Med Chem. 2013;13:584-94 pubmed
    Focal adhesion kinase (FAK), hyaluronan (HA), and hyaluronan synthase-3 (HAS3) have been implicated in cancer growth and progression...
  21. Viola M, Brüggemann K, Karousou E, Caon I, Caravà E, Vigetti D, et al. MDA-MB-231 breast cancer cell viability, motility and matrix adhesion are regulated by a complex interplay of heparan sulfate, chondroitin-/dermatan sulfate and hyaluronan biosynthesis. Glycoconj J. 2017;34:411-420 pubmed publisher
    ..to HGF and an increase in the synthesis of hyaluronan, due to an upregulation of the hyaluronan synthases HAS2 and HAS3. Interestingly, EXT1-depleted cells showed a downregulation of the UDP-sugar transporter SLC35D1, whereas SLC35D2 ..
  22. Malaisse J, Pendaries V, Hontoir F, De Glas V, Van Vlaender D, Simon M, et al. Hyaluronan Does Not Regulate Human Epidermal Keratinocyte Proliferation and Differentiation. J Biol Chem. 2016;291:6347-58 pubmed publisher
    Hyaluronan (HA) is synthesized by three HA synthases (HAS1, HAS2, and HAS3) and secreted in the extracellular matrix. In human skin, large amounts of HA are found in the dermis...
  23. Gerber P, Buhren B, Schrumpf H, Hevezi P, Bölke E, Sohn D, et al. Mechanisms of skin aging induced by EGFR inhibitors. Support Care Cancer. 2016;24:4241-8 pubmed publisher
    ..treated with erlotinib in vitro showed a significant down-modulation of hyaluronan synthases (HAS2 and HAS3), whereas senescence-associated genes (p21, p53, IL-6, maspin) were upregulated, along with a G1 cell cycle arrest ..
  24. Leger K, Cushing Haugen K, Hansen J, Fan W, Leisenring W, Martin P, et al. Clinical and Genetic Determinants of Cardiomyopathy Risk among Hematopoietic Cell Transplantation Survivors. Biol Blood Marrow Transplant. 2016;22:1094-1101 pubmed publisher
    ..reported genetic associations among early-onset cardiomyopathy cases, including rs1786814 in CELF4, rs2232228 in HAS3, and rs17863783 in UGT1A6. None of these markers were associated with risk of late-onset cardiomyopathy...
  25. do Nascimento Pedrosa T, De Vuyst E, Mound A, Lambert de Rouvroit C, Maria Engler S, Poumay Y. Methyl-β-cyclodextrin treatment combined to incubation with interleukin-4 reproduces major features of atopic dermatitis in a 3D-culture model. Arch Dermatol Res. 2017;309:63-69 pubmed publisher
    ..Carbonic anhydrase II (CA2) and hyaluronan synthase 3 (HAS3), two other markers up-regulated in AD, were also induced when MβCD treatment was followed by IL-..
  26. Parida R, Samanta L. In silico analysis of candidate proteins sharing homology with Streptococcus agalactiae proteins and their role in male infertility. Syst Biol Reprod Med. 2017;63:15-28 pubmed publisher
    ..AA: amino acid; ASA: antisperm antibodies; GBS: group B streptococcus; HLA: human leukocyte antigen; HAS3: hyaluronan synthase 3: IEDB: immune epitope database; MAPO2: O6-methylguanine-induced apoptosis 2; MHC: major ..
  27. Yang G, Jiang B, Cai W, Liu S, Zhao S. Hyaluronan and hyaluronan synthases expression and localization in embryonic mouse molars. J Mol Histol. 2016;47:413-20 pubmed publisher
    ..Furthermore, HAS1 and HAS2 expression decreased, while HAS3 expression increased from E13.5 to E18.5...
  28. Li Y, Li Z, Jin T, Wang Z, Zhao P. Tau Pathology Promotes the Reorganization of the Extracellular Matrix and Inhibits the Formation of Perineuronal Nets by Regulating the Expression and the Distribution of Hyaluronic Acid Synthases. J Alzheimers Dis. 2017;57:395-409 pubmed publisher
    ..Here, we showed that HA synthases (HASs), including Has1, Has2, and Has3, were widely expressed in murine central nervous system...
  29. Ouyang X, Panetta N, Talbott M, Payumo A, Halluin C, Longaker M, et al. Hyaluronic acid synthesis is required for zebrafish tail fin regeneration. PLoS ONE. 2017;12:e0171898 pubmed publisher
    ..transcriptional profiling and whole-mount expression analyses of zebrafish larvae, we have identified hyaluronan synthase 3 (has3) as an upregulated gene during caudal fin regeneration...
  30. Panogeorgou T, Tserbini E, Filou S, Vynios D, Naxakis S, Papadas T, et al. Hyaluronan synthases and hyaluronidases in nasal polyps. Eur Arch Otorhinolaryngol. 2016;273:1801-8 pubmed publisher
    ..Moreover, HAS2 and HAS3 were the only hyaluronan synthases detected, the expression of which was almost similar in NPs and NM...
  31. Morita T, Fujikawa K, Baba O, Shibata S. An in situ hybridization study of Hyaluronan synthase (Has) mRNA in developing mouse molar and incisor tooth germs. Gene Expr Patterns. 2016;21:28-40 pubmed publisher
    ..0 to 18.0 in both molar and incisor tooth germs, but disappeared after birth. Meanwhile, Has3 mRNA was exclusively expressed within the enamel organ, especially in the inner enamel epithelium (IEE), stellate ..
  32. Nagase H, Kudo D, Suto A, Yoshida E, Suto S, Negishi M, et al. 4-Methylumbelliferone Suppresses Hyaluronan Synthesis and Tumor Progression in SCID Mice Intra-abdominally Inoculated With Pancreatic Cancer Cells. Pancreas. 2017;46:190-197 pubmed publisher
    ..In vitro, MU inhibited pericellular HA matrix formation; however, HAS3 mRNA was up-regulated. Treatment with 0.5 mM MU suppressed cellular proliferation by 26.4%, migration by 14...
  33. Della Colleta H, Carvalho H. Hyaluronan Content and Distribution in the Rat Ventral Prostate after Castration. Biochem Cell Biol. 2018;: pubmed publisher
    ..qRT-PCR also showed that Has1 and Has2 mRNA increased transiently after castration, whereas Has3 mRNA declined markedly...
  34. Jokela T, Kärnä R, Rauhala L, Bart G, Pasonen Seppänen S, Oikari S, et al. Human Keratinocytes Respond to Extracellular UTP by Induction of Hyaluronan Synthase 2 Expression and Increased Hyaluronan Synthesis. J Biol Chem. 2017;292:4861-4872 pubmed publisher
    ..10-100 μm UTP strongly up-regulated HAS2 expression, although the other hyaluronan synthases (HAS1, HAS3) and hyaluronidases (HYAL1, HYAL2) were not affected...
  35. Koistinen V, Kärnä R, Koistinen A, Arjonen A, Tammi M, Rilla K. Cell protrusions induced by hyaluronan synthase 3 (HAS3) resemble mesothelial microvilli and share cytoskeletal features of filopodia. Exp Cell Res. 2015;337:179-91 pubmed publisher
    ..that the protrusions on rat peritoneal surface are ultrastructurally indistinguishable from those induced by GFP-HAS3 in MCF-7 cells...
  36. Li L, Qi L, Liang Z, Song W, Liu Y, Wang Y, et al. Transforming growth factor-β1 induces EMT by the transactivation of epidermal growth factor signaling through HA/CD44 in lung and breast cancer cells. Int J Mol Med. 2015;36:113-22 pubmed publisher
    ..Furthermore, we found that TGF-β1 upregulated the expression of hyaluronan synthases (HAS1, HAS2 and HAS3) and promoted the expression of CD44, a cell surface receptor for HA, which interacts with EGFR, resulting in the ..
  37. Ueta M, Sotozono C, Kinoshita S. Expression of interleukin-4 receptor ? in human corneal epithelial cells. Jpn J Ophthalmol. 2011;55:405-410 pubmed publisher
    ..protein 1 (RASGRP1), carbonic anhydrase II (CA2), cytokine-inducible SH2-containing protein (CISH), hyaluronan synthase 3 (HAS3), calpain 14 (CAPN14), endothelin receptor type A (EDNRA), cathepsin C (CTSC), and lecithin retinol ..
  38. Fischer J. Role of hyaluronan in atherosclerosis: Current knowledge and open questions. Matrix Biol. 2018;: pubmed publisher
    ..One example being the induction of HAS3 by interleukin-1β and other cytokines...
  39. NGUYEN N, Kumar A, Chacko S, Ouellette R, Ghosh A. Human hyaluronic acid synthase-1 promotes malignant transformation via epithelial-to-mesenchymal transition, micronucleation and centrosome abnormalities. Cell Commun Signal. 2017;15:48 pubmed publisher
    ..hyaluronic acid (HA) molecules are synthesized by three membrane spanning Hyaluronic Acid Synthases (HAS1, HAS2 and HAS3). Of the three, HAS1 is found to be localized more into the cytoplasmic space where it synthesizes intracellular HA...
  40. Kultti A, Zhao C, Singha N, Zimmerman S, Osgood R, Symons R, et al. Accumulation of extracellular hyaluronan by hyaluronan synthase 3 promotes tumor growth and modulates the pancreatic cancer microenvironment. Biomed Res Int. 2014;2014:817613 pubmed publisher
    ..Overexpression of HAS3 increased hyaluronan synthesis in BxPC-3 pancreatic cancer cells...
  41. Kuroda K, Utani A, Hamasaki Y, Shinkai H. Up-regulation of putative hyaluronan synthase mRNA by basic fibroblast growth factor and insulin-like growth factor-1 in human skin fibroblasts. J Dermatol Sci. 2001;26:156-60 pubmed
    Recently, cDNAs for the three putative human hyaluronan synthase (HAS) genes, HAS1, HAS2 and HAS3, have been cloned...
  42. Sayo T, Sugiyama Y, Takahashi Y, Ozawa N, Sakai S, Ishikawa O, et al. Hyaluronan synthase 3 regulates hyaluronan synthesis in cultured human keratinocytes. J Invest Dermatol. 2002;118:43-8 pubmed
    Three human hyaluronan synthase genes (HAS1, HAS2, and HAS3) have been cloned, but the functional differences between these HAS genes remains obscure...
  43. Jacobson A, Brinck J, Briskin M, Spicer A, Heldin P. Expression of human hyaluronan synthases in response to external stimuli. Biochem J. 2000;348 Pt 1:29-35 pubmed
    In the present study we have investigated the expression of mRNAs for hyaluronan synthase isoforms (HAS1, HAS2 and HAS3) in different cells in response to various stimuli...
  44. Spicer A, Seldin M, Olsen A, Brown N, Wells D, Doggett N, et al. Chromosomal localization of the human and mouse hyaluronan synthase genes. Genomics. 1997;41:493-7 pubmed
    ..Three highly conserved related genes have been identified, designated HAS1, HAS2, and HAS3 in humans and Has1, Has2, and Has3 in the mouse...
  45. Deen A, Rilla K, Oikari S, Kärnä R, Bart G, Häyrinen J, et al. Rab10-mediated endocytosis of the hyaluronan synthase HAS3 regulates hyaluronan synthesis and cell adhesion to collagen. J Biol Chem. 2014;289:8375-89 pubmed publisher
    ..Rab10 colocalized with HAS3 in intracellular vesicular structures and was co-immunoprecipitated with HAS3 from isolated endosomal vesicles...
  46. Dunn K, Lee P, Wilson C, Iida J, Wasiluk K, Hugger M, et al. Inhibition of hyaluronan synthases decreases matrix metalloproteinase-7 (MMP-7) expression and activity. Surgery. 2009;145:322-9 pubmed publisher
    Hyaluronan (HA) and its biosynthetic enzymes hyaluronan synthases (HAS2 and HAS3) mediate Matrigel invasion by SW620 colon carcinoma cells...
  47. Wang S, Zhen L, Liu Z, Ai Q, Ji Y, Du G, et al. Identification and analysis of the promoter region of the human HAS3 gene. Biochem Biophys Res Commun. 2015;460:1008-14 pubmed publisher
    ..matrix that is synthesized at the plasma membrane by the hyaluronan synthases including HAS1, HAS2 and HAS3. The expression and regulation of HAS1-3 are implicated in numerous physiological and pathological processes...
  48. Takabe P, Bart G, Ropponen A, Rilla K, Tammi M, Tammi R, et al. Hyaluronan synthase 3 (HAS3) overexpression downregulates MV3 melanoma cell proliferation, migration and adhesion. Exp Cell Res. 2015;337:1-15 pubmed publisher
    ..In this study we produced a MV3 melanoma cell line with inducible expression of the hyaluronan synthase 3 (HAS3) and studied its effect on the behavior of the melanoma cells...
  49. Chang I, Liang P, Li C, Wu W, Huang C, Lin V, et al. HAS3 underexpression as an indicator of poor prognosis in patients with urothelial carcinoma of the upper urinary tract and urinary bladder. Tumour Biol. 2015;36:5441-50 pubmed publisher
    Via data mining a published transcriptomic database of UBUC (GSE31684), we discovered hyaluronan synthase-3 (HAS3) as the most significant gene stepwise downregulated from early tumorigenesis to progression among those associated with ..
  50. Deen A, Arasu U, Pasonen Seppänen S, Hassinen A, Takabe P, Wojciechowski S, et al. UDP-sugar substrates of HAS3 regulate its O-GlcNAcylation, intracellular traffic, extracellular shedding and correlate with melanoma progression. Cell Mol Life Sci. 2016;73:3183-204 pubmed publisher
    ..For the very first time, the present study demonstrated a rapid recycling of HAS3 between PM and endosomes, controlled by the cytosolic levels of the HAS substrates UDP-GlcUA and UDP-GlcNAc...
  51. Homann S, Grandoch M, Kiene L, Podsvyadek Y, Feldmann K, Rabausch B, et al. Hyaluronan synthase 3 promotes plaque inflammation and atheroprogression. Matrix Biol. 2018;66:67-80 pubmed publisher
    ..Here the role of HA synthase 3 (HAS3) in atheroprogression was studied...
  52. Pacheco Costa R, Kadakia J, Atkinson E, Wallace J, Plotkin L, Reginato R. Connexin37 deficiency alters organic bone matrix, cortical bone geometry, and increases Wnt/?-catenin signaling. Bone. 2017;97:105-113 pubmed publisher
    ..of Cx37 increased genes involved in collagen maturation (loxl3 and loxl4) and glycosaminoglycans- (chsy1, chpf and has3) proteoglycans- associated genes (biglycan and decorin)...
  53. Malaisse J, Bourguignon V, De Vuyst E, Lambert de Rouvroit C, Nikkels A, Flamion B, et al. Hyaluronan metabolism in human keratinocytes and atopic dermatitis skin is driven by a balance of hyaluronan synthases 1 and 3. J Invest Dermatol. 2014;134:2174-2182 pubmed publisher
    ..glycosaminoglycan synthesized directly into the extracellular matrix by three hyaluronan synthases (HAS1, HAS2, and HAS3). HA is abundantly synthesized by keratinocytes but its epidermal functions remain unclear...
  54. Twarock S, Freudenberger T, Poscher E, Dai G, Jannasch K, Dullin C, et al. Inhibition of oesophageal squamous cell carcinoma progression by in vivo targeting of hyaluronan synthesis. Mol Cancer. 2011;10:30 pubmed publisher
    ..of 4-methylumbelliferone (4-MU), an inhibitor of HA-synthesis, and of lentiviral knock down of HA-synthase 3 (HAS3), the main HAS isoform in the human ESCC tissues and the human ESCC cell line used in this study, were determined...
  55. Viola M, Bartolini B, Vigetti D, Karousou E, Moretto P, Deleonibus S, et al. Oxidized low density lipoprotein (LDL) affects hyaluronan synthesis in human aortic smooth muscle cells. J Biol Chem. 2013;288:29595-603 pubmed publisher
    ..9 ± 5.6. OxLDL treatments doubled the transcripts of HA synthase HAS2 and HAS3. Accumulated HA stimulated migration of aortic smooth muscle cells and monocyte adhesiveness to extracellular ..
  56. Wang X, Liu W, Sun C, Armenian S, Hakonarson H, Hageman L, et al. Hyaluronan synthase 3 variant and anthracycline-related cardiomyopathy: a report from the children's oncology group. J Clin Oncol. 2014;32:647-53 pubmed publisher
    ..a matched case-control design (93 cases, 194 controls), we identified a common SNP, rs2232228, in the hyaluronan synthase 3 (HAS3) gene that exerts a modifying effect on anthracycline dose-dependent cardiomyopathy risk (P = 5...
  57. Bullard K, Kim H, Wheeler M, Wilson C, Neudauer C, Simpson M, et al. Hyaluronan synthase-3 is upregulated in metastatic colon carcinoma cells and manipulation of expression alters matrix retention and cellular growth. Int J Cancer. 2003;107:739-46 pubmed
    ..HA and its biosynthetic enzymes (HAS1, HAS2 and HAS3) are thought to participate in tumor growth and cancer progression...
  58. Gesteira T, Sun M, Coulson Thomas Y, Yamaguchi Y, Yeh L, Hascall V, et al. Hyaluronan Rich Microenvironment in the Limbal Stem Cell Niche Regulates Limbal Stem Cell Differentiation. Invest Ophthalmol Vis Sci. 2017;58:4407-4421 pubmed publisher
    ..synthesized by hyaluronan synthases (HASs), and vertebrates have the following three types: HAS1, HAS2, and HAS3. Wild-type and HAS and TSG-6 knockout mice-HAS1-/-;HAS3-/-, HAS2Δ/ΔCorEpi, TSG-6-/--were used to determine the ..
  59. Perkins K, Arranz A, Yamaguchi Y, HRABETOVA S. Brain extracellular space, hyaluronan, and the prevention of epileptic seizures. Rev Neurosci. 2017;28:869-892 pubmed publisher
    ..Head trauma, ischemic stroke, and other brain insults that initiate epileptogenesis are known to be associated with an early decrease in high-molecular-weight HA, and preventing that decrease in HA may prevent the epileptogenesis...
  60. Keller K, Sun Y, Yang Y, Bradley J, Acott T. Perturbation of hyaluronan synthesis in the trabecular meshwork and the effects on outflow facility. Invest Ophthalmol Vis Sci. 2012;53:4616-25 pubmed publisher
    ..Three HA synthase genes (HAS1-3) have been identified. Here, we evaluate the contribution of each of the HAS proteins to outflow facility in anterior segment perfusion culture...
  61. Siiskonen H, Poukka M, Tyynelä Korhonen K, Sironen R, Pasonen Seppänen S. Inverse expression of hyaluronidase 2 and hyaluronan synthases 1-3 is associated with reduced hyaluronan content in malignant cutaneous melanoma. BMC Cancer. 2013;13:181 pubmed publisher
    ..These results provide new information about hyaluronan metabolism in benign, premalignant and malignant melanocytic tumors of the skin. ..
  62. Grskovic B, Pollaschek C, Mueller M, Stuhlmeier K. Expression of hyaluronan synthase genes in umbilical cord blood stem/progenitor cells. Biochim Biophys Acta. 2006;1760:890-5 pubmed
    ..mRNA for HAS1 is undetectable but HAS3 mRNA can be readily detected in freshly isolated CD133+ as well as in CD133- UCB cells...
  63. Suzuki K, Yamamoto T, Usui T, Suzuki K, Heldin P, Yamashita H. Expression of hyaluronan synthase in intraocular proliferative diseases: regulation of expression in human vascular endothelial cells by transforming growth factor-beta. Jpn J Ophthalmol. 2003;47:557-64 pubmed
  64. Selbi W, de La Motte C, Hascall V, Day A, Bowen T, Phillips A. Characterization of hyaluronan cable structure and function in renal proximal tubular epithelial cells. Kidney Int. 2006;70:1287-95 pubmed
    ..Overexpression of HAS3 is associated with induction of HA cable formation, and also increased incorporation of HA into pericellular coats...
  65. Campo G, Avenoso A, Campo S, Angela D, Ferlazzo A, Calatroni A. TNF-alpha, IFN-gamma, and IL-1beta modulate hyaluronan synthase expression in human skin fibroblasts: synergistic effect by concomital treatment with FeSO4 plus ascorbate. Mol Cell Biochem. 2006;292:169-78 pubmed
    ..and IL-1beta were added to normal or/and exposed to FeSO(4) plus ascorbate fibroblast cultures and HAS1, HAS2 and HAS3 mRNA content, by PCR-real time, was assayed 3,h later. HA levels were also evaluated after 24,h incubation...
  66. Nykopp T, Rilla K, Tammi M, Tammi R, Sironen R, Hamalainen K, et al. Hyaluronan synthases (HAS1-3) and hyaluronidases (HYAL1-2) in the accumulation of hyaluronan in endometrioid endometrial carcinoma. BMC Cancer. 2010;10:512 pubmed publisher
    ..mechanism of hyaluronan accumulation, we examined the expression levels of the hyaluronan synthases (HAS1, HAS2 and HAS3) and hyaluronidases (HYAL1 and HYAL2), and correlated them with hyaluronan content and HAS1-3 immunoreactivity...
  67. Simpson M, Wilson C, Furcht L, Spicer A, Oegema T, McCarthy J. Manipulation of hyaluronan synthase expression in prostate adenocarcinoma cells alters pericellular matrix retention and adhesion to bone marrow endothelial cells. J Biol Chem. 2002;277:10050-7 pubmed
    ..PC3M-LN4 cells stably transfected with antisense HAS2 and HAS3 failed to form pericellular matrices...
  68. Simpson M, Reiland J, Burger S, Furcht L, Spicer A, Oegema T, et al. Hyaluronan synthase elevation in metastatic prostate carcinoma cells correlates with hyaluronan surface retention, a prerequisite for rapid adhesion to bone marrow endothelial cells. J Biol Chem. 2001;276:17949-57 pubmed
    ..Up-regulation of HA synthase isoforms Has2 and Has3 relative to levels expressed by normal prostate corresponded to elevated HA synthesis and avid BMEC adhesion...
  69. Nair S, Phillips A, Norton N, Spurlock G, Williams H, Craig K, et al. Further evidence for the association of MMP9 with nephropathy in type 2 diabetes and application of DNA pooling technology to candidate gene screening. J Nephrol. 2008;21:400-5 pubmed
    ..generation and can modulate its signal transduction activity; renal HA is synthesised by HA synthases HAS2 and HAS3. We report the first screening of the genes encoding HAS2 and HAS3 for sequence variants predisposing to ..
  70. Compagnone M, Gatti V, Presutti D, Ruberti G, Fierro C, Markert E, et al. ?Np63-mediated regulation of hyaluronic acid metabolism and signaling supports HNSCC tumorigenesis. Proc Natl Acad Sci U S A. 2017;114:13254-13259 pubmed publisher
    ..sustaining the production of HA levels in cell culture and in vivo by regulating the expression of the HA synthase HAS3 and two hyaluronidase genes, HYAL-1 and HYAL-3...
  71. Song J, Molla K, Anandharaj A, Cornax I, O Sullivan M, Kirtane A, et al. Triptolide suppresses the in vitro and in vivo growth of lung cancer cells by targeting hyaluronan-CD44/RHAMM signaling. Oncotarget. 2017;8:26927-26940 pubmed publisher
    ..lung cancer (NSCLC) cells, the proliferation and self-renewal of pulmospheres, and levels of HA synthase 2 (HAS2), HAS3, HA, CD44, RHAMM, EGFR, Akt and ERK, but increased the cleavage of caspase 3 and PARP...
  72. Tzellos T, Kyrgidis A, Vahtsevanos K, Triaridis S, Printza A, Klagas I, et al. Nodular basal cell carcinoma is associated with increased hyaluronan homeostasis. J Eur Acad Dermatol Venereol. 2011;25:679-87 pubmed publisher
    ..Nodular BCC is associated with increased levels of HA concomitant with upregulation of gene expression of HAS3, HYAL3 and RHAMM, when compared with normal adjacent skin...
  73. Kuo Y, Fang W, Huang C, Tsai S, Wang Y, Yang C, et al. Hyaluronan synthase 3 mediated oncogenic action through forming inter-regulation loop with tumor necrosis factor alpha in oral cancer. Oncotarget. 2017;8:15563-15583 pubmed publisher
    ..However, its role and mediation in oral cancer remains elusive. Hyaluronan synthase 3 (HAS3), involved in pro-inflammatory short chain HA synthesis, was the predominant synthase in oral cancer ..