Complement 3 is involved in changing the phenotype of human glomerular mesangial cells

Jian Xin Wan, Noboru Fukuda, Morito Endo, Yoshiko Tahira, En Hui Yao, Hiroyuki Matsuda, Takahiro Ueno, Koichi Matsumoto

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)


Complement activation contributes to tissue injury in various forms of glomerulopathy and is characterized by deposition of complement component, 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 gowth and phenotype of mesangial cells. Cultured human mesangial cells (HMCs) expressed C3 mRNA and protein, and levels were increased in response to IFN-γ and TNF-α. 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 type I αI (collagen IV) mRNAs, which are markers of the synthetic phenotype. C3a decreased expression of α-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.

Original languageEnglish
Pages (from-to)495-501
Number of pages7
JournalJournal of Cellular Physiology
Issue number2
Publication statusPublished - Nov 2007


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