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  • Title: Serotonin enhances the production of type IV collagen by human mesangial cells.
    Author: Kasho M, Sakai M, Sasahara T, Anami Y, Matsumura T, Takemura T, Matsuda H, Kobori S, Shichiri M.
    Journal: Kidney Int; 1998 Oct; 54(4):1083-92. PubMed ID: 9767524.
    Abstract:
    BACKGROUND: The plasma concentration of 5-hydroxytryptamine (5-HT) in diabetic patients is higher than that in normal subjects. Since recent reports have demonstrated the presence of 5-HT2A receptor in glomerular mesangial cells, it is possible that 5-HT may be involved in the development of diabetic nephropathy through the 5-HT2A receptor in mesangial cells. Because expansion of the glomerular mesangial lesion is a characteristic feature of diabetic nephropathy, we examined the effect of 5-HT on the production of type IV collagen by human mesangial cells. METHODS: Human mesangial cells were incubated with 5-HT with or without 5-HT receptor antagonists, protein kinase C (PKC) inhibitor or transforming growth factor-beta (TGF-beta) antibody. Type IV collagen mRNA and protein concentration in medium were measured by Northern blot analysis and enzyme-linked immunosorbent assay (ELISA), respectively. TGF-beta mRNA and bioactivity in the medium were measured by Northern blot analysis and bioassay using mink lung epithelial cells, respectively. RESULTS: 5-HT stimulated the production of type IV collagen by human mesangial cells, which was inhibited by ketanserin and sarpogrelate hydrochloride, 5-HT2A receptor antagonists, but not by ondansetron, a 5-HT3 receptor antagonist. 5-HT increased the bioactivities of both active and total TGF-beta. However, the 5-HT-enhanced production of type IV collagen was completely inhibited by an anti-TGF-beta antibody. Furthermore, a PKC inhibitor, calphostin C, inhibited the 5-HT-induced increase in type IV collagen secretion, and the activity of membrane PKC was increased by 5-HT. Phorbol ester activated type IV collagen production as well as active and total TGF-beta. Calphostin C completely inhibited the 5-HT-enhanced activity of active TGF-beta, but did not inhibit exogenous TGF-beta-induced increase in type IV collagen secretion. CONCLUSIONS: Our results suggest that 5-HT-enhanced production of type IV collagen by human mesangial cells is mediated by activation of PKC and subsequent increase in active TGF-beta activity.
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