HAS1

Summary

Gene Symbol: HAS1
Description: hyaluronan synthase 1
Alias: HAS, hyaluronan synthase 1, HA synthase 1, hyaluronate synthase 1, hyaluronic acid synthase 1
Species: human
Products:     HAS1

Top Publications

  1. Adamia S, Treon S, Reiman T, Tournilhac O, McQuarrie C, Mant M, et al. Potential impact of a single nucleotide polymorphism in the hyaluronan synthase 1 gene in Waldenstrom's macroglobulinemia. Clin Lymphoma. 2005;5:253-6 pubmed
    The hyaluronan synthase 1 (HAS1) gene encodes a plasma membrane protein that synthesizes hyaluronan, an extracellular matrix molecule...
  2. 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
    ..possible 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 ..
  3. Adamia S, Reichert A, Kuppusamy H, Kriangkum J, Ghosh A, Hodges J, et al. Inherited and acquired variations in the hyaluronan synthase 1 (HAS1) gene may contribute to disease progression in multiple myeloma and Waldenstrom macroglobulinemia. Blood. 2008;112:5111-21 pubmed publisher
    To characterize genetic contributions toward aberrant splicing of the hyaluronan synthase 1 (HAS1) gene in multiple myeloma (MM) and Waldenstrom macroglobulinemia (WM), we sequenced 3616 bp in HAS1 exons and introns involved in aberrant ..
  4. Ghosh A, Kuppusamy H, Pilarski L. Aberrant splice variants of HAS1 (Hyaluronan Synthase 1) multimerize with and modulate normally spliced HAS1 protein: a potential mechanism promoting human cancer. J Biol Chem. 2009;284:18840-50 pubmed publisher
    ..We have identified a family of aberrant splice variants of HAS1 (the hyaluronan synthase 1 gene) in some B lineage cancers, characterized by exon skipping and/or partial intron retention events ..
  5. Golshani R, Lopez L, Estrella V, Kramer M, Iida N, Lokeshwar V. Hyaluronic acid synthase-1 expression regulates bladder cancer growth, invasion, and angiogenesis through CD44. Cancer Res. 2008;68:483-91 pubmed publisher
    ..HA is synthesized by HA synthases HAS1, HAS2, or HAS3...
  6. Kramer M, Escudero D, Lokeshwar S, Golshani R, Ekwenna O, Acosta K, et al. Association of hyaluronic acid family members (HAS1, HAS2, and HYAL-1) with bladder cancer diagnosis and prognosis. Cancer. 2011;117:1197-209 pubmed publisher
    ..003), lymph node invasion (P = .033), HYAL-1 (P = .019), and HAS1 (P = .027) transcript levels, and HYAL-1 staining (P = .021) were independently associated with metastasis...
  7. Adamia S, Reiman T, Crainie M, Mant M, Belch A, Pilarski L. Intronic splicing of hyaluronan synthase 1 (HAS1): a biologically relevant indicator of poor outcome in multiple myeloma. Blood. 2005;105:4836-44 pubmed
    In this study, we show that the hyaluronan synthase 1 (HAS1) gene undergoes aberrant intronic splicing in multiple myeloma (MM)...
  8. Adamia S, Pilarski P, Belch A, Pilarski L. Genetic abnormalities in Waldenström's macroglobulinemia. Clin Lymphoma Myeloma. 2009;9:30-2 pubmed publisher
    ..By intensive sequencing of the hyaluronan synthase 1 (HAS1) gene in malignant and normal cells from patients with WM, we have identified both types of mutation ..
  9. Adamia S, Crainie M, Kriangkum J, Mant M, Belch A, Pilarski L. Abnormal expression of hyaluronan synthases in patients with Waldenstrom's macroglobulimenia. Semin Oncol. 2003;30:165-8 pubmed
    ..Three isoenzymes of HAS-HAS1, HAS2, and HAS3-are detected in humans. Aberrant expression of the HASs is coupled with different abnormalities...

More Information

Publications97

  1. Yabushita H, Kishida T, Fusano K, Kanyama K, Zhuo L, Itano N, et al. Role of hyaluronan and hyaluronan synthase in endometrial cancer. Oncol Rep. 2005;13:1101-5 pubmed
    ..from 59 endometrial cancer patients were immunostained by the avidin-biotin-peroxidase complex method using anti-HAS1, anti-HAS2, anti-HAS3 and anti-CD44 antibody...
  2. Tammi M, Oikari S, Pasonen Seppänen S, Rilla K, Auvinen P, Tammi R. Activated hyaluronan metabolism in the tumor matrix - Causes and consequences. Matrix Biol. 2018;: pubmed publisher
    ..Increased expression of the genes of hyaluronan synthases (HAS1-3) are infrequent in human tumors, while posttranslational modifications that activate the HAS enzymes, and glucose ..
  3. Brüning L, Hackert P, Martin R, Davila Gallesio J, Aquino G, Urlaub H, et al. RNA helicases mediate structural transitions and compositional changes in pre-ribosomal complexes. Nat Commun. 2018;9:5383 pubmed publisher
    ..Our data support roles for Has1 in triggering release of the U14 snoRNP, a critical event during early 40S maturation, and in driving assembly of ..
  4. 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 development of adult ..
  5. Yang L, Zhang S, Guo K, Huang H, Qi S, Yao J, et al. miR-125a restrains cell migration and invasion by targeting STAT3 in gastric cancer cells. Onco Targets Ther. 2019;12:205-215 pubmed publisher
    ..of miR-125a and the expression relevance of signal transducer and activator of transcription 3 (STAT3) and hyaluronan synthase 1 (HAS1)...
  6. Furfari A, Wan B, Ding K, Wong A, Zhu L, Bezjak A, et al. Genetic biomarkers associated with pain flare and dexamethasone response following palliative radiotherapy in patients with painful bone metastases. Ann Palliat Med. 2017;6:S240-S247 pubmed publisher
    ..Significant SNVs associated with dexamethasone response were from genes involved in extracellular matrix (HAS1, ADAMTS16) and cytoskeleton regulation (GAS2L2)...
  7. Wang G, Zhao W, Gao X, Zhang D, Li Y, Zhang Y, et al. HNF1A‑AS1 promotes growth and metastasis of esophageal squamous cell carcinoma by sponging miR‑214 to upregulate the expression of SOX-4. Int J Oncol. 2017;51:657-667 pubmed publisher
    ..HNF1A‑AS1 (HAS1), a long non-coding RNA (lncRNA), has been identified prevalently involved in various human cancers...
  8. 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
    ..The present study was designed to investigate the expression of HA and three isoforms of HASs (HAS1, 2, 3) in embryonic mouse molars...
  9. Buravkova L, Andreeva E, Lobanova M, Cotnezova E, Grigoriev A. The Differential Expression of Adhesion Molecule and Extracellular Matrix Genes in Mesenchymal Stromal Cells after Interaction with Cord Blood Hematopoietic Progenitors. Dokl Biochem Biophys. 2018;479:69-71 pubmed publisher
    ..a downregulation of the genes encoding the majority of matrix molecules (SPP1; COL6A2,7A1; MMP1,3; TIMP1,3; and HAS1) and cell-matrix adhesion molecules (ITGs) was revealed...
  10. 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
    ..vertebrate extracellular matrix that is synthesized at the plasma membrane by the hyaluronan synthases including HAS1, HAS2 and HAS3...
  11. 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
    ..Staining for HAS1-3 and CD44 proteins was most intense in the granulosa layer...
  12. Alpantaki K, Zafiropoulos A, Tseliou M, Vasarmidi E, Sourvinos G. Herpes simplex virus type-1 infection affects the expression of extracellular matrix components in human nucleus pulposus cells. Virus Res. 2019;259:10-17 pubmed publisher
    ..Furthermore, collagen type II expression was completely abolished. HAS1 expression was not affected, whereas HAS 2 and 3 were found to be significantly reduced...
  13. 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
    Vesicular trafficking of hyaluronan synthases (HAS1-3) from endoplasmic reticulum (ER) through Golgi to plasma membrane (PM), and either back to endosomes and lysosomes, or out into extracellular vesicles, is important for their ..
  14. Andreeva E, Andrianova I, Sotnezova E, Gornostaeva A, Khorkova S, Buravkova L. Hematopoiesis-supportive function of growth-arrested human adipose-tissue stromal cells under physiological hypoxia. J Biosci Bioeng. 2019;127:647-654 pubmed publisher
    ..ICAM1, HCAM/CD44) and cell-matrix adhesion (ITGs), extracellular matrix production (COLs) and remodeling (MMPs, HAS1) in growth-arrested ASCs at physiological hypoxia in comparison with ambient O2 (20%)...
  15. 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
    In vertebrates, hyaluronan is produced in the plasma membrane from cytosolic UDP-sugar substrates by hyaluronan synthase 1-3 (HAS1-3) isoenzymes that transfer N-acetylglucosamine (GlcNAc) and glucuronic acid (GlcUA) in alternative ..
  16. Mehić M, de Sá V, Hebestreit S, Heldin C, Heldin P. The deubiquitinating enzymes USP4 and USP17 target hyaluronan synthase 2 and differentially affect its function. Oncogenesis. 2017;6:e348 pubmed publisher
    ..prominent in the extracellular matrix, is balanced through the actions of hyaluronan-synthesizing enzymes (HAS1, 2 and 3) and degrading hyaluronidases (Hyal 1, 2, 3 and PH20)...
  17. 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...
  18. Simon J, DiCarlo L, Kruger C, Johnson W, Kappen C, Richards B. Gene expression in salivary glands: effects of diet and mouse chromosome 17 locus regulating macronutrient intake. Physiol Rep. 2015;3: pubmed publisher
    Dcpp2, Prrt1, and Has1 are plausible candidate genes for the Mnic1 (macronutrient intake-carbohydrate) locus on mouse chromosome 17, based on their map positions and sequence variants, documented expression in salivary glands, and the ..
  19. Dai L, Chen Y, Bonstaff K, Doyle L, Toole B, Parsons C, et al. Induction of hyaluronan production by oncogenic KSHV and the contribution to viral pathogenesis in AIDS patients. Cancer Lett. 2015;362:158-66 pubmed publisher
    ..de novo infection induces HA production from primary endothelial cells through upregulation of HA synthase gene 1 (Has1) and a multifunctional glycoprotein, CD147...
  20. 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...
  21. Chan D, Xiao W, Li J, de La Motte C, Sandy J, Plaas A. Deficiency of hyaluronan synthase 1 (Has1) results in chronic joint inflammation and widespread intra-articular fibrosis in a murine model of knee joint cartilage damage. Osteoarthritis Cartilage. 2015;23:1879-89 pubmed publisher
    ..in wild-type (WT) mice, we investigated a role for HA in the response to cartilage injury in mice lacking HA synthase 1 (Has1(-/-)). Femoral groove cartilage of WT and Has1(-/-) mice was debrided to generate a non-bleeding wound...
  22. 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
    ..In scarred vocal folds, expression of Has1 and Has2 increased at day 3 together with expression of HA and returned to normal at 2 weeks...
  23. Han Y, Zhang J, Hu C. A systematic toxicity evaluation of cephalosporins via transcriptomics in zebrafish and in silico ADMET studies. Food Chem Toxicol. 2018;116:264-271 pubmed publisher
    ..The transcriptional levels of the has1 and cnnm2a genes, which are related to embryo development and absorption of Mg2+ in vivo, significantly changed...
  24. Della Colleta H, Carvalho H. Hyaluronan Content and Distribution in the Rat Ventral Prostate after Castration. Biochem Cell Biol. 2018;: pubmed publisher
    ..qRT-PCR showed that Has1 and 2 are major synthases and that Hyal 1 was the predominant hydrolase expressed in the VP...
  25. Ismail H, Miotla Zarebska J, Troeberg L, Tang X, Stott B, Yamamoto K, et al. Brief Report: JNK-2 Controls Aggrecan Degradation in Murine Articular Cartilage and the Development of Experimental Osteoarthritis. Arthritis Rheumatol. 2016;68:1165-71 pubmed publisher
    ..These included Has1, Adamts4, Tnf, Il6, Il18, Il18rap, Il1a, Inhba, Cd68, Ngf, Ccr2, Wnt16, and Tnfaip6, but not Adamts5...
  26. Valkonen M, Haapasalo H, Rilla K, Tyynelä Korhonen K, Soini Y, Pasonen Seppänen S. Elevated expression of hyaluronan synthase 2 associates with decreased survival in diffusely infiltrating astrocytomas. BMC Cancer. 2018;18:664 pubmed publisher
    ..The TMA sections were stained for hyaluronan, CD44, hyaluronan synthases 1-3 (HAS1-3) and hyaluronidase 2 (HYAL2)...
  27. 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 ..
  28. 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, ..
  29. 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
    ..In the present study, we examined expression patterns of Has1, -2, -3 mRNA in developing mouse molar and incisor tooth germs from embryonic day (E) 11...
  30. Fouladi Nashta A, Raheem K, Marei W, Ghafari F, Hartshorne G. Regulation and roles of the hyaluronan system in mammalian reproduction. Reproduction. 2017;153:R43-R58 pubmed
    ..Its biosynthesis by HA synthase (HAS1-3) and catabolism by hyaluronidases (HYALs) are affected by ovarian steroid hormones...
  31. 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...
  32. Khoshnevis S, Askenasy I, Johnson M, Dattolo M, Young Erdos C, Stroupe M, et al. The DEAD-box Protein Rok1 Orchestrates 40S and 60S Ribosome Assembly by Promoting the Release of Rrp5 from Pre-40S Ribosomes to Allow for 60S Maturation. PLoS Biol. 2016;14:e1002480 pubmed publisher
    ..Rok1 inactivation arises because Rrp5 release is blocked and implicate a previously undescribed interaction between Rrp5 and the DEAD-box protein Has1 in mediating snR30 accumulation when Rrp5 release from pre-40S subunits is blocked.
  33. Li F, Hao P, Liu G, Wang W, Han R, Jiang Z, et al. Effects of 4-methylumbelliferone and high molecular weight hyaluronic acid on the inflammation of corneal stromal cells induced by LPS. Graefes Arch Clin Exp Ophthalmol. 2017;255:559-566 pubmed publisher
    ..LPS stimulation caused the up-regulation of HAS1 and HAS2 expression in corneal fibroblasts...
  34. Osiecka Iwan A, Moskalewski S, Hyc A. Influence of IGF1, TGF?1, bFGF and G-CSF/M-CSF on the mRNA levels of selected matrix proteins, cytokines, metalloproteinase 3 and TIMP1 in rat synovial membrane cells. Folia Histochem Cytobiol. 2016;54:159-165 pubmed publisher
    ..containing cartilage interstitial fluid (CIF) responded by changes in the expression of hyaluronan synthases (HAS1 and HAS2), collagen type I, versican, aggrecan, lubricin, matrix metalloproteinases 2 and 3 (MMP2 and MMP3), tissue ..
  35. Fowke T, Karunasinghe R, Bai J, Jordan S, Gunn A, Dean J. Hyaluronan synthesis by developing cortical neurons in vitro. Sci Rep. 2017;7:44135 pubmed publisher
    ..In the relative absence of glia, neurons exhibited HAS1-3 mRNA at all time-points...
  36. 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
    ..It was found that rat mesothelium in vivo is positive for hyaluronan and Has1-3...
  37. 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...
  38. Hayashi S, Kuramata M, Abe T, Takagi H, Ozawa K, Ishikawa S. Phytochelatin synthase OsPCS1 plays a crucial role in reducing arsenic levels in rice grains. Plant J. 2017;91:840-848 pubmed publisher
    ..Using a forward genetic approach, we isolated two rice mutants (has1 and has2) in which As levels were much higher in grains but significantly lower in node I compared with the wild ..
  39. 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
    ..Hyaluronan synthesis requires the transport of hyaluronan synthases (HAS1-3) from Golgi to plasma membrane (PM), where the enzymes are activated...
  40. 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...
  41. 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...
  42. 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
    ..Breast density and mammographic features were correlated with the localization and expression of HA, CD44, and HAS1-3 isoforms, and their combined effect on patients' survivals was explored...
  43. Stocco E, Barbon S, Radossi P, Rajendran S, Dalzoppo D, Bortolami M, et al. Autologous chondrocytes as a novel source for neo-chondrogenesis in haemophiliacs. Cell Tissue Res. 2016;366:51-61 pubmed publisher
    ..synthesis of the extracellular matrix proteins of the articular cartilage (ACAN, COL1A, COL2A, COL10A, COL9A, COMP, HAS1, SOX9), although the over-expression of COL1A1, COL10A1, COMP and HAS was observed...
  44. 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)...
  45. Oikari S, Kettunen T, Tiainen S, Häyrinen J, Masarwah A, Sudah M, et al. UDP-sugar accumulation drives hyaluronan synthesis in breast cancer. Matrix Biol. 2018;67:63-74 pubmed publisher
    ..Interestingly, hyaluronan content did not correlate with the mRNA levels of the hyaluronan synthases (HAS1-3), thus emphasizing the role of the UDP-sugar substrates of these enzymes...
  46. Tiainen S, Oikari S, Tammi M, Rilla K, Hamalainen K, Tammi R, et al. High extent of O-GlcNAcylation in breast cancer cells correlates with the levels of HAS enzymes, accumulation of hyaluronan, and poor outcome. Breast Cancer Res Treat. 2016;160:237-247 pubmed
    ..A high extent of cytoplasmic O-GlcNAcylation correlated also with the accumulation of all hyaluronan synthase (HAS1-3) proteins and with a large amount of HA in the tumor stroma...
  47. Albrecht C, Schlegel W, Eckl P, Jagersberger T, Sadeghi K, Berger A, et al. Alterations in CD44 isoforms and HAS expression in human articular chondrocytes during the de- and re-differentiation processes. Int J Mol Med. 2009;23:253-9 pubmed
    ..Expression levels of CD44s, CD44-lt, CD44-st, HAS1, HAS2, HAS3 and UDPGD were determined by real-time RT-PCR at different time points...
  48. 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
    ..IFN-gamma, 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...
  49. 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
    ..The role of hyaluronan in melanoma progression including benign nevi and lymph node metastases has not been investigated earlier, nor the details of its synthesis and degradation...
  50. Chen L, Neville R, Michael D, Martin J, Luo D, Thomas D, et al. Identification and analysis of the human hyaluronan synthase 1 gene promoter reveals Smad3- and Sp3-mediated transcriptional induction. Matrix Biol. 2012;31:373-9 pubmed publisher
    ..In the present study, we investigated the mechanism of HAS1 transcriptional up-regulation in response to these cytokines...
  51. Calabro A, Oken M, Hascall V, Masellis A. Characterization of hyaluronan synthase expression and hyaluronan synthesis in bone marrow mesenchymal progenitor cells: predominant expression of HAS1 mRNA and up-regulated hyaluronan synthesis in bone marrow cells derived from multiple myeloma pati. Blood. 2002;100:2578-85 pubmed
    ..Of the 3 Has isoforms, Has1 mRNA was expressed predominantly in myeloma bmMPCs, with expression 7.6-fold greater than Has2...
  52. 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
    ..elucidate the 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 ..
  53. 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
    ..lines requires a pericellular hyaluronan (HA) matrix and correlates with dramatically up-regulated HA synthase (HAS) expression...
  54. Mian N. Analysis of cell-growth-phase-related variations in hyaluronate synthase activity of isolated plasma-membrane fractions of cultured human skin fibroblasts. Biochem J. 1986;237:333-42 pubmed
    ..The corresponding protein of stationary-growth-phase cells, which expressed much higher nucleotide-sugar-precursor-binding activity, appeared to have lost its oligosaccharide-synthesizing activity. ..
  55. Kao J. The NF-kappaB inhibitor pyrrolidine dithiocarbamate blocks IL-1beta induced hyaluronan synthase 1 (HAS1) mRNA transcription, pointing at NF-kappaB dependence of the gene HAS1. Exp Gerontol. 2006;41:641-7 pubmed
    ..Herein, evidence is provided that in type-B synoviocytes (TBS) HAS1 is a gene that depends on the transcription factor nuclear factor kappa B (NF-kappaB) for its activation...
  56. Siiskonen H, Kärnä R, Hyttinen J, Tammi R, Tammi M, Rilla K. Hyaluronan synthase 1 (HAS1) produces a cytokine-and glucose-inducible, CD44-dependent cell surface coat. Exp Cell Res. 2014;320:153-63 pubmed publisher
    ..In mammals, three hyaluronan synthase isoenzymes (HAS1-3) inserted in the plasma membrane produce hyaluronan directly on cell surface...
  57. Campo G, Avenoso A, Campo S, D Ascola A, Ferlazzo A, Calatroni A. Differential effect of growth factors on hyaluronan synthase gene expression in fibroblasts exposed to oxidative stress. Biochemistry (Mosc). 2007;72:974-82, 4 p. pubmed
    The aim of this study was to evaluate how growth factors (PDGF-BB, EGF, and TGF-1beta) modulate hyaluronan synthase (HAS) activities in normal or stressed cultured human skin fibroblasts...
  58. Li L, Asteriou T, Bernert B, Heldin C, Heldin P. Growth factor regulation of hyaluronan synthesis and degradation in human dermal fibroblasts: importance of hyaluronan for the mitogenic response of PDGF-BB. Biochem J. 2007;404:327-36 pubmed
    ..showed that PDGF-BB treatment induced a 3-fold increase in the already high level of HAS2 mRNA, and increases in HAS1 and HYAL1 mRNA, whereas the levels of HAS3 and HYAL2 mRNA were not affected...
  59. Berdiaki A, Nikitovic D, Tsatsakis A, Katonis P, Karamanos N, Tzanakakis G. bFGF induces changes in hyaluronan synthase and hyaluronidase isoform expression and modulates the migration capacity of fibrosarcoma cells. Biochim Biophys Acta. 2009;1790:1258-65 pubmed publisher
    ..Transfection with siHAS2 and siHAS1 showed that mainly HAS1 synthesized high molecular weight HA regulates HT1080 cell motility...
  60. Hamada S, Nishida Y, Zhuo L, Shinomura T, Ikuta K, Arai E, et al. Suppression of hyaluronan synthesis attenuates the tumorigenicity of low grade chondrosarcoma. J Orthop Res. 2017;: pubmed publisher
    ..No significant changes in mRNA expression of Has1-3 were observed. Furthermore, MU inhibited the growth of grafted tumors in vivo...
  61. Spicer A, Nguyen T. Mammalian hyaluronan synthases: investigation of functional relationships in vivo. Biochem Soc Trans. 1999;27:109-15 pubmed
  62. Itano N, Kimata K. Molecular cloning of human hyaluronan synthase. Biochem Biophys Res Commun. 1996;222:816-20 pubmed
    ..4% and 96.0% identity in nucleotide sequence and amino acid sequences, respectively. Northern analysis indicated that the gene was ubiquitously expressed in various human tissues. ..
  63. Freudenberger T, Röck K, Dai G, Dorn S, Mayer P, Heim H, et al. Estradiol inhibits hyaluronic acid synthase 1 expression in human vascular smooth muscle cells. Basic Res Cardiol. 2011;106:1099-109 pubmed publisher
    ..In contrast, HAS2- and HAS3-mRNA-expression were not affected. This E(2)-mediated effect on HAS1 mRNA-expression was accompanied by reduced hyaluronan secretion and a shift of HA toward lower molecular weight as ..
  64. Tzuman Y, Sapoznik S, Granot D, Nevo N, Neeman M. Peritoneal adhesion and angiogenesis in ovarian carcinoma are inversely regulated by hyaluronan: the role of gonadotropins. Neoplasia. 2010;12:51-60 pubmed
    ..Accordingly, angiogenesis of the adhered spheroids was significantly elevated in DON-treated tumors. These results can explain the selective pressure that can lead to simultaneously increased tumor expression of both HASs and Hyals...
  65. Stuhlmeier K, Pollaschek C. Adenovirus-mediated gene transfer of mutated IkappaB kinase and IkappaBalpha reveal NF-kappaB-dependent as well as NF-kappaB-independent pathways of HAS1 activation. J Biol Chem. 2005;280:42766-73 pubmed
    ..furthermore, that the only gene that readily responds to stimulation with a series of proinflammatory cytokines is HAS1. Here we probe the involvement of the transcription factor NF-kappaB in induced and noninduced HAS activation...
  66. 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
    ..We sought to determine the genes affected by HAS and FAK inhibition and hypothesized that dual inhibition would synergistically inhibit viability...
  67. Kriangkum J, Warkentin A, Warkinton A, Belch A, Pilarski L. Alteration of introns in a hyaluronan synthase 1 (HAS1) minigene convert Pre-mRNA [corrected] splicing to the aberrant pattern in multiple myeloma (MM): MM patients harbor similar changes. PLoS ONE. 2013;8:e53469 pubmed publisher
    Aberrant pre-mRNA splice variants of hyaluronan synthase 1 (HAS1) have been identified in malignant cells from cancer patients. Bioinformatic analysis suggests that intronic sequence changes can underlie aberrant splicing...
  68. 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
    ..HA) is naturally synthesized by hyaluronan synthases (HASs), and vertebrates have the following three types: HAS1, HAS2, and HAS3...
  69. 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
    ..Furthermore, HAS1 and HAS2 exhibited differential expression in VECs and non-VECs populating intraocular proliferative membranes...
  70. 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
    ..However, the contribution of HA to human outflow resistance remains unclear. Three HA synthase genes (HAS1-3) have been identified...
  71. 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...
  72. Nishio K, Ozawa Y, Ito H, Kifune T, Narita T, Iinuma T, et al. Functional expression of BMP7 receptors in oral epithelial cells. Interleukin-17F production in response to BMP7. J Recept Signal Transduct Res. 2017;37:515-521 pubmed publisher
    ..The microarray analysis revealed the induction of interleukin-17 F (IL-17 F), netrin G2 (NTNG2) and hyaluronan synthase 1 (HAS1). Luciferase assay using the 5'-UTR of the IL-17 F gene revealed transcriptional regulation...
  73. 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...
  74. 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
    ..HA) is a 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...
  75. Vigetti D, Genasetti A, Karousou E, Viola M, Clerici M, Bartolini B, et al. Modulation of hyaluronan synthase activity in cellular membrane fractions. J Biol Chem. 2009;284:30684-94 pubmed publisher
    ..In mammals, HA is synthesized by three homologous HA synthases, HAS1, HAS2, and HAS3, that polymerize the HA chain using UDP-glucuronic acid and UDP-N-acetylglucosamine as precursors...
  76. 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
    Mammals have three homologous genes encoding proteins with hyaluronan synthase activity (Has1-3), all producing an identical polymer from UDP-N-acetylglucosamine and UDP-glucuronic acid...
  77. Kyossev Z, Weigel P. An enzyme capture assay for analysis of active hyaluronan synthases. Anal Biochem. 2007;371:62-70 pubmed
    ..Specific HAS proteins (e.g., HAS1, not HAS2 or HAS3) captured in this pull-down approach are readily immunodetected by Western blot analysis using ..
  78. Meran S, Thomas D, Stephens P, Martin J, Bowen T, Phillips A, et al. Involvement of hyaluronan in regulation of fibroblast phenotype. J Biol Chem. 2007;282:25687-97 pubmed
    ..In dermal fibroblasts, differentiation was associated with an induction of HA synthase (HAS1 and HAS2) transcription and assembly of pericellular HA coats...
  79. Shyjan A, Heldin P, Butcher E, Yoshino T, Briskin M. Functional cloning of the cDNA for a human hyaluronan synthase. J Biol Chem. 1996;271:23395-9 pubmed
    ..In addition, hyaluronan has been implicated as an important substrate for migration of adhesion of leukocytes during inflammation...
  80. Akgul Y, Holt R, Mummert M, Word A, Mahendroo M. Dynamic changes in cervical glycosaminoglycan composition during normal pregnancy and preterm birth. Endocrinology. 2012;153:3493-503 pubmed publisher
    ..by an increase in HA resulting from differential expression of the HA synthase (Has) genes, with increased Has1 in preterm in contrast to Has2 induction at term. The Has2 gene but not Has1 is regulated in part by estrogen...
  81. Stuhlmeier K. Hyaluronan production in synoviocytes as a consequence of viral infections: HAS1 activation by Epstein-Barr virus and synthetic double- and single-stranded viral RNA analogs. J Biol Chem. 2008;283:16781-9 pubmed publisher
    ..Real time reverse transcription-PCR data show that HAS1 mRNA levels are significantly elevated in virus-treated cells, whereas mRNA levels for the genes HAS2 and HAS3 ..
  82. 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
    Human hyaluronic acid (HA) molecules are synthesized by three membrane spanning Hyaluronic Acid Synthases (HAS1, HAS2 and HAS3)...
  83. Sano K, Gotoh M, Dodo K, Tajima N, Shimizu Y, Murakami Murofushi K. Age-related changes in cyclic phosphatidic acid-induced hyaluronic acid synthesis in human fibroblasts. Hum Cell. 2018;31:72-77 pubmed publisher
    ..The expression of HAS1, 3, hyaluronidase-1, and -2 did not change with aging...
  84. Chang M, Kang I, Gale M, MANICONE A, Kinsella M, Braun K, et al. Versican is produced by Trif- and type I interferon-dependent signaling in macrophages and contributes to fine control of innate immunity in lungs. Am J Physiol Lung Cell Mol Physiol. 2017;313:L1069-L1086 pubmed publisher
    ..The signaling events regulating versican are distinct from those for hyaluronan synthase 1 (HAS1) and syndecan-4 in macrophages. HAS1 expression requires TLR2 and MyD88...
  85. Kuppusamy H, Ogmundsdottir H, Baigorri E, Warkentin A, Steingrimsdottir H, Haraldsdottir V, et al. Inherited polymorphisms in hyaluronan synthase 1 predict risk of systemic B-cell malignancies but not of breast cancer. PLoS ONE. 2014;9:e100691 pubmed publisher
    Genetic variations in the hyaluronan synthase 1 gene (HAS1) influence HAS1 aberrant splicing...
  86. Midgley A, Bowen T. Analysis of human hyaluronan synthase gene transcriptional regulation and downstream hyaluronan cell surface receptor mobility in myofibroblast differentiation. Methods Mol Biol. 2015;1229:605-18 pubmed publisher
    ..Defining the mechanisms regulating expression of the human hyaluronan synthase (HAS) genes that encode the corresponding HA-synthesizing HAS enzymes is therefore important in the context of HA ..
  87. Nagaoka A, Yoshida H, Nakamura S, Morikawa T, Kawabata K, Kobayashi M, et al. Regulation of Hyaluronan (HA) Metabolism Mediated by HYBID (Hyaluronan-binding Protein Involved in HA Depolymerization, KIAA1199) and HA Synthases in Growth Factor-stimulated Fibroblasts. J Biol Chem. 2015;290:30910-23 pubmed publisher
    ..Stimulation of HAS1/2 expression and suppression of HYBID expression by TGF-β1 were abrogated by blockade of the MAPK and/or Smad ..
  88. Poukka M, Bykachev A, Siiskonen H, Tyynelä Korhonen K, Auvinen P, Pasonen Seppänen S, et al. Decreased expression of hyaluronan synthase 1 and 2 associates with poor prognosis in cutaneous melanoma. BMC Cancer. 2016;16:313 pubmed publisher
    ..We have previously shown that synthesis of hyaluronan and expression of its synthases 1-2 (HAS1-2) decrease in cutaneous melanoma, compared to benign melanocytic lesions...