Serotonin enhances the production of type IV collagen by human mesangial cells

• Published in: Kidney international Vol. 54; no. 4; pp. 1083 - 1092
• Main Authors: Kasho, Masaya, Sakai, Masakazu, Sasahara, Takayuki, Anami, Yoshichika, Matsumura, Takeshi, Takemura, Toru, Matsuda, Hirofumi, Kobori, Shozo, Shichiri, Motoaki
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.10.1998; Nature Publishing
• Subjects: Biological and medical sciences; Cells, Cultured; Collagen - biosynthesis; Diabetic Nephropathies - etiology; Diabetic Nephropathies - metabolism; diabetic nephropathy; Glomerular Mesangium - drug effects; Glomerular Mesangium - metabolism; human mesangial cell; Humans; Investigative techniques, diagnostic techniques (general aspects); Ketanserin - pharmacology; Kinetics; Medical sciences; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; protein kinase C; Protein Kinase C - metabolism; Receptor, Serotonin, 5-HT2A; Receptors, Serotonin - drug effects; Receptors, Serotonin - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; serotonin; Serotonin - pharmacology; Serotonin Antagonists - pharmacology; Succinates - pharmacology; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; transforming growth factor-β; type IV collagen; Urinary system; type IV collagen; serotonin; human mesangial cell; transforming growth factor-β; protein kinase C; diabetic nephropathy; Human; Cell culture; Exploration; Serotonin; Mesangial cell; Collagen
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1046/j.1523-1755.1998.00114.x

Serotonin enhances the production of type IV collagen by human mesangial cells. 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. Human mesangial cells were incubated with 5-HT with or without 5-HT receptor antagonists, protein kinase C (PKC) inhibitor or transforming growth factor-β (TGF-β) antibody. Type IV collagen mRNA and protein concentration in medium were measured by Northern blot analysis and enzyme-linked immunosorbent assay (ELISA), respectively. TGF-β mRNA and bioactivity in the medium were measured by Northern blot analysis and bioassay using mink lung epithelial cells, respectively. 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-β. However, the 5-HT-enhanced production of type IV collagen was completely inhibited by an anti-TGF-β 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-β. Calphostin C completely inhibited the 5-HT-enhanced activity of active TGF-β, but did not inhibit exogenous TGF-β-induced increase in type IV collagen secretion. 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-β activity.