title: Complement 3 is involved in changing the phenotype of human glomerular mesangial cells.
abstract: Complement activation contributes to tissue injury in various forms of glomerulopathy and is characterized by deposition of complement components, which accelerates the progression of chronic renal damage. We recently reported that complement 3 (C3), a critical component of the complement system, is associated with the synthetic phenotype of vascular smooth muscle cells. It is possible that C3 stimulates mesangial cells to assume the synthetic phenotype to, in turn, induce glomerular injury and sclerosis. We investigated the role of C3 in the growth and phenotype of mesangial cells. Cultured human mesangial cells (HMCs) expressed C3 mRNA and protein, and levels were increased in response to IFN-gamma and TNF-alpha. HMCs also expressed C3a receptor mRNA and protein. Exogenous C3a stimulated DNA synthesis in HMCs in a dose-dependent manner. C3a decreased expression h-caldesmon mRNA, a marker of the contractile phenotype, and increased the expression of osteopontin, matrix Gla, and collagen type1 alpha1 (collagen IV) mRNAs, which are markers of the synthetic phenotype. C3a decreased expression of alpha-smooth muscle actin in HMCs. Small interfering RNA (siRNA) targeting C3 reduced the DNA synthesis and proliferation of HMCs, increased expression of h-caldesmon mRNA, and decreased expression of osteopontin, matrix Gla, and collagen IV mRNAs in HMCs. These results indicate that C3 causes HMCs to convert to the synthetic phenotype and stimulates growth of mesangial cells, suggesting that C3 may play an important role in phenotypic regulation of mesangial cells in renal diseases.
authors.affiliation: Department of Medicine, Division of Nephrology and Endocrinology, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Wan
authors.forename: Noboru
authors.initials: N
authors.lastname: Fukuda
authors.forename: Morito
authors.initials: M
authors.lastname: Endo
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Tahira
authors.forename: En-Hui
authors.initials: EH
authors.lastname: Yao
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsuda
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ueno
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsumoto
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D003176:Complement C3 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015926:Complement C3a / Q000235:genetics / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D050527:Mesangial Cells / Q000166:cytology* / Q000276:immunology; D010641:Phenotype; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011951:Receptors, Complement / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D015415:Biomarkers; D003176:Complement C3; D007155:Immunologic Factors; D034741:RNA, Small Interfering; D011951:Receptors, Complement; D014409:Tumor Necrosis Factor-alpha; D015926:Complement C3a; D007371:Interferon-gamma