Gene Symbol: Has2
Description: hyaluronan synthase 2
Alias: hyaluronan synthase 2, HA synthase 2, hyaluronate synthase 2, hyaluronic acid synthase 2
Species: rat
Products:     Has2

Top Publications

  1. Itano N, Sawai T, Yoshida M, Lenas P, Yamada Y, Imagawa M, et al. Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties. J Biol Chem. 1999;274:25085-92 pubmed
    Three mammalian hyaluronan synthase genes, HAS1, HAS2, and HAS3, have recently been cloned. In this study, we characterized and compared the enzymatic properties of these three HAS proteins...
  2. Vigetti D, Genasetti A, Karousou E, Viola M, Moretto P, Clerici M, et al. Proinflammatory cytokines induce hyaluronan synthesis and monocyte adhesion in human endothelial cells through hyaluronan synthase 2 (HAS2) and the nuclear factor-kappaB (NF-kappaB) pathway. J Biol Chem. 2010;285:24639-45 pubmed publisher
    ..This signaling pathway mediated hyaluronan synthase 2 (HAS2) mRNA expression without altering other glycosaminoglycan metabolism...
  3. Karvinen S, Pasonen Seppänen S, Hyttinen J, Pienimäki J, Törrönen K, Jokela T, et al. Keratinocyte growth factor stimulates migration and hyaluronan synthesis in the epidermis by activation of keratinocyte hyaluronan synthases 2 and 3. J Biol Chem. 2003;278:49495-504 pubmed
    ..of intermediate size hyaluronan in the culture medium and within keratinocytes, and a rapid increase of hyaluronan synthase 2 (Has2) mRNA, suggesting a direct influence on this gene...
  4. Ohno T, French L, Hirano S, Ossoff R, Rousseau B. Effect of hepatocyte growth factor on gene expression of extracellular matrix during wound healing of the injured rat vocal fold. Ann Otol Rhinol Laryngol. 2008;117:696-702 pubmed
    ..Results provide evidence of HGF treatment effects on procollagen type III and HAS-2 gene expression pathways. ..
  5. Falconi D, Aubin J. LIF inhibits osteoblast differentiation at least in part by regulation of HAS2 and its product hyaluronan. J Bone Miner Res. 2007;22:1289-300 pubmed
    ..To test this hypothesis, we further analyzed the function of one of the genes identified, hyaluronan synthase 2 (HAS2), in the LIF-induced inhibition...
  6. Bernert B, Porsch H, Heldin P. Hyaluronan synthase 2 (HAS2) promotes breast cancer cell invasion by suppression of tissue metalloproteinase inhibitor 1 (TIMP-1). J Biol Chem. 2011;286:42349-59 pubmed publisher
    ..capacity compared with MDA-MB-231 cells predominately due to an increased expression of hyaluronan synthase 2 (HAS2)...
  7. Ohno T, Hirano S, Kanemaru S, Yamashita M, Umeda H, Suehiro A, et al. Expression of extracellular matrix proteins in the vocal folds and bone marrow derived stromal cells of rats. Eur Arch Otorhinolaryngol. 2008;265:669-74 pubmed
    ..The mRNA expression of ECM components (type I procollagen, decorin, Has2, CD44, MMP-1, and GAPDH) were examined in cultured BSCs and the vocal fold mucosa by the reverse transcription-..
  8. Saavalainen K, Pasonen Seppänen S, Dunlop T, Tammi R, Tammi M, Carlberg C. The human hyaluronan synthase 2 gene is a primary retinoic acid and epidermal growth factor responding gene. J Biol Chem. 2005;280:14636-44 pubmed
    ..We found that in REK cells EGF and all-trans-RA up-regulated hyaluronan synthase 2 (Has2) gene expression within 2 h 4-fold each and in HaCaT human immortal keratinocytes 8- and 33-fold, ..
  9. Ohno T, Hirano S, Rousseau B. Extracellular matrix gene expression during wound healing of the injured rat vocal fold. Otolaryngol Head Neck Surg. 2009;140:757-61 pubmed publisher
    ..Knowledge of the temporal regulation of these genes and underlying histology will be used in future studies to investigate molecular approaches for manipulation of vocal fold injury. ..

More Information


  1. Rügheimer L, Carlsson C, Johnsson C, Hansell P. Renal hyaluronan content during experimental uncontrolled diabetes in rats. J Physiol Pharmacol. 2008;59:115-28 pubmed
    ..The inability to respond to a water load with further diuresis may be related to the already elevated papillary hyaluronan and the inability to change hyaluronan during water loading. ..
  2. Huang Y, Askew E, Knudson C, Knudson W. CRISPR/Cas9 knockout of HAS2 in rat chondrosarcoma chondrocytes demonstrates the requirement of hyaluronan for aggrecan retention. Matrix Biol. 2016;56:74-94 pubmed publisher
    ..HA synthase-2 (Has2)-specific single guide RNA was introduced into two different variant lines of rat chondrosarcoma chondrocytes; ..
  3. 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...
  4. Takahashi N, Tarumi W, Ishizuka B. Involvement of hyaluronan synthesis in ovarian follicle growth in rats. Reproduction. 2014;147:189-97 pubmed publisher
    ..were expressed in the ovaries of perinatal, prepubertal, and adult rats, and the expression levels of Has1 and Has2 genes were modulated during the estrous cycle in adult rats and following administration of exogenous gonadotropins ..
  5. Rügheimer L, Olerud J, Johnsson C, Takahashi T, Shimizu K, Hansell P. Hyaluronan synthases and hyaluronidases in the kidney during changes in hydration status. Matrix Biol. 2009;28:390-5 pubmed publisher
    ..Reduced HAS 2 gene expression and increased excreted urinary hyaluronidase activity during dehydration contribute to the reduced amount of hyaluronan and to antidiuretic response. ..
  6. Rauhala L, Hämäläinen L, Salonen P, Bart G, Tammi M, Pasonen Seppänen S, et al. Low dose ultraviolet B irradiation increases hyaluronan synthesis in epidermal keratinocytes via sequential induction of hyaluronan synthases Has1-3 mediated by p38 and Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling. J Biol Chem. 2013;288:17999-8012 pubmed publisher
    ..In contrast, Has2 and Has3 were persistently elevated from 8 h onward...
  7. Rosines E, Schmidt H, Nigam S. The effect of hyaluronic acid size and concentration on branching morphogenesis and tubule differentiation in developing kidney culture systems: potential applications to engineering of renal tissues. Biomaterials. 2007;28:4806-17 pubmed
  8. Rilla K, Lammi M, Sironen R, Törrönen K, Luukkonen M, Hascall V, et al. Changed lamellipodial extension, adhesion plaques and migration in epidermal keratinocytes containing constitutively expressed sense and antisense hyaluronan synthase 2 (Has2) genes. J Cell Sci. 2002;115:3633-43 pubmed
    ..the importance of hyaluronan synthesis in keratinocytes by establishing cell lines carrying the exogenous hyaluronan synthase 2 (Has2) gene in sense and antisense orientations to increase and decrease their hyaluronan synthesis, ..
  9. Pasonen Seppänen S, Karvinen S, Törrönen K, Hyttinen J, Jokela T, Lammi M, et al. EGF upregulates, whereas TGF-beta downregulates, the hyaluronan synthases Has2 and Has3 in organotypic keratinocyte cultures: correlations with epidermal proliferation and differentiation. J Invest Dermatol. 2003;120:1038-44 pubmed
    ..This was associated with upregulation of the hyaluronan synthases Has2 and Has3, and the hyaluronan receptor CD44...
  10. Camenisch T, Spicer A, Brehm Gibson T, Biesterfeldt J, Augustine M, Calabro A, et al. Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme. J Clin Invest. 2000;106:349-60 pubmed
    We identified hyaluronan synthase-2 (Has2) as a likely source of hyaluronan (HA) during embryonic development, and we used gene targeting to study its function in vivo...
  11. Hellman U, Hellström M, Morner S, Engström Laurent A, Aberg A, Oliviero P, et al. Parallel up-regulation of FGF-2 and hyaluronan during development of cardiac hypertrophy in rat. Cell Tissue Res. 2008;332:49-56 pubmed publisher
    ..Expression of the genes coding for hyaluronan synthase 1 (HAS1), HAS2, HAS3, CD44, fibroblast growth factor-2 (FGF-2), and FGF receptor-1 (FGFR-1) and the histological evidence for ..
  12. Törrönen K, Nikunen K, Kärnä R, Tammi M, Tammi R, Rilla K. Tissue distribution and subcellular localization of hyaluronan synthase isoenzymes. Histochem Cell Biol. 2014;141:17-31 pubmed publisher
    ..The three HAS isoenzymes (HAS1, HAS2, and HAS3) expressed in mammalian cells differ in their enzymatic properties and regulation by external stimuli, ..
  13. Maroski J, Vorderwülbecke B, Fiedorowicz K, Da Silva Azevedo L, Siegel G, Marki A, et al. Shear stress increases endothelial hyaluronan synthase 2 and hyaluronan synthesis especially in regard to an atheroprotective flow profile. Exp Physiol. 2011;96:977-86 pubmed publisher
    ..This study was undertaken to reveal whether endothelial hyaluronan synthesis via hyaluronan synthase 2 (HAS2) can be changed by different shear stress conditions in vitro, especially in regard to an ..
  14. Moffatt P, Lee E, St Jacques B, Matsumoto K, Yamaguchi Y, Roughley P. Hyaluronan production by means of Has2 gene expression in chondrocytes is essential for long bone development. Dev Dyn. 2011;240:404-12 pubmed publisher
    Mice possessing no Has2 expression in chondrocytes died near birth and displayed abnormalities throughout their skeleton. By embryonic day 18...
  15. Oishi Y, Kato H, Noguchi T. Dietary protein as a potent regulator of the hyaluronan synthase gene in rat skin. Biosci Biotechnol Biochem. 2003;67:736-42 pubmed
    ..These results suggest that protein malnutrition has a primary impact on the gene expression of rhass, which leads to the reduction of hyaluronan content and to disfunction of the skin. ..
  16. Yokoyama U, Minamisawa S, Quan H, Ghatak S, Akaike T, Segi Nishida E, et al. Chronic activation of the prostaglandin receptor EP4 promotes hyaluronan-mediated neointimal formation in the ductus arteriosus. J Clin Invest. 2006;116:3026-34 pubmed
    ..Activation of EP4, adenylyl cyclase, and PKA all increased HA production and the level of HA synthase 2 (HAS2) transcripts. In immature rat DA explants, ICF was promoted by EP4/PKA stimuli...
  17. Declèves A, Caron N, Voisin V, Legrand A, Bouby N, Kultti A, et al. Synthesis and fragmentation of hyaluronan in renal ischaemia. Nephrol Dial Transplant. 2012;27:3771-81 pubmed publisher
    ..Thereafter, HAS1 tended to normalize, while HAS2 increased steadily. Both synthetic enzymes were localized around tubules and in the interstitium...
  18. Ormiston M, Slaughter G, Deng Y, Stewart D, Courtman D. The enzymatic degradation of hyaluronan is associated with disease progression in experimental pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2010;298:L148-57 pubmed publisher
    ..Expression of HA synthase 2 (HAS2) was elevated in MCT-challenged animals at 24 and 28 days, consistent with increased synthesis of HMM HA...
  19. Kabilova N, Bondar A, Ivanova L. Expression of type II hyaluronan-synthase gene in kidneys Wistar and Brattleboro rats with diabetes insipidus: effect of vasopressin and its analogues. Dokl Biochem Biophys. 2009;425:61-4 pubmed
  20. Wang H, Zhan Y, Xu L, Feuerstein G, Wang X. Use of suppression subtractive hybridization for differential gene expression in stroke: discovery of CD44 gene expression and localization in permanent focal stroke in rats. Stroke. 2001;32:1020-7 pubmed
    ..Northern blotting and real-time polymerase chain reaction were used to evaluate the expression of CD44 and hyaluronan synthase 2 (HAS-2) mRNA...
  21. 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
    ..mRNA expression 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...