Expression of human hyaluronan synthases in response to external stimuli

Abstract

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. Human mesothelial cells, which synthesize large amounts of hyaluronan, express mRNAs encoding all three HAS isoforms, whereas their transformed counterparts, mesothelioma cells, which produce only minute amounts of hyaluronan, express only HAS3 mRNA. Human lung fibroblasts and the glioma cell line U-118 MG express only the HAS2 and HAS3 genes. The expression of the transcripts was higher in subconfluent than in confluent cultures and was well correlated with the production of hyaluronan by the cells. Stimulation of mesothelial cells with platelet-derived growth factor-BB induced an up-regulation of mRNA for HAS2 to a maximum after 6 h of stimulation; HAS1 and HAS3 genes were only induced slightly. Transforming growth factor-beta1 reduced HAS2 mRNA slightly, and hydrocortisone reduced it strongly, within 6 h of stimulation in mesothelial cell cultures but did not significantly affect the expression of mRNAs for HAS1 and HAS3. Induction of HAS1 and HAS2 protein levels in response to the stimuli above correlated with HAS transcript levels. Thus the expression of the three HAS isoforms is more prominent in growing cells than in resting cells and is differentially regulated by various stimuli suggesting distinct functional roles of the three proteins.

Temporal effects of cytokine treatment on lubricant synthesis and matrix metalloproteinase activity of fibroblast-like synoviocytes

“…For example, HA greater than 600 kDA has significant anti‐inflammatory effects on FLS and OA chondrocytes; meanwhile HA of 1.6 MDa or greater promotes Collagen II production in chondrocytes (Bauer et al, ; Wang, Lin, Chiang, Lin, & Hou, ). HA oligomer fragments, however, are both products and activators of proinflammatory mediators in joint pathologies (P. Ghosh, ; S. Ghosh et al, ; Itano et al, ; Jacobson, Brinck, Briskin, Spicer, & Heldin, ). We confirmed that HA greater than 3 MDa is best produced when IL‐1β, TNF‐α, and TGF‐β1 are all supplemented (Blewis et al, ).…”

Molecular Changes in Mesothelioma With an Impact on Prognosis and Treatment

“…Hyaluronan is an important constituent of the extracellular matrix. PDGF-BB-stimulated normal human mesothelial cells express both hyaluronan synthase and hyaluronan [115][116] .…”

Hyaluronan and morphogenesis

“…HA biosynthesis can be stimulated by many growth factors and cytokines. In the vast majority of cases, transcriptional upregulation of HAS2 appears to be the preferred mechanism for stimulation of HA biosynthesis (Jacobsen et al, 1999; Kaback and Smith, 1999; Elvin et al, 1999; Nishida et al, 2000; Karvinen et al, 2003; Pasonen‐Seppanen et al, 2003; Tanimoto et al, 2001). HAS2 expression is upregulated by the transforming growth factor‐beta (TGF‐β)/bone morphogenetic protein (BMP) superfamily members, interleukin‐1 beta (IL‐1β), tumor necrosis factor‐alpha (TNF‐α), epidermal growth factor (EGF), keratinocyte growth factor (KGF), and many other factors.…”

“…HAS2 expression is upregulated by the transforming growth factor‐beta (TGF‐β)/bone morphogenetic protein (BMP) superfamily members, interleukin‐1 beta (IL‐1β), tumor necrosis factor‐alpha (TNF‐α), epidermal growth factor (EGF), keratinocyte growth factor (KGF), and many other factors. HAS2 is potently inhibited by glucocorticoids, through a combination of transcriptional repression and increased mRNA turnover (Jacobsen et al, 1999; Zhang et al, 2000). HAS2 is the key enzyme in several adult tissues, such as the dermis and the ovaries (Fulop et al, 1997; Sugiyama et al, 1998).…”