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Activin A Is a Potent Activator of Renal Interstitial Fibroblasts

Shin Yamashita^*, Akito Maeshima^*,, Itaru Kojima and Yoshihisa Nojima^*

*Third Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan; and Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan

Correspondence to Dr. Akito Maeshima, Third Department of Internal Medicine, Gunma University School of Medicine, 3-39-15 Showa, Maebashi 371-8511, Japan. Phone: +81-272-220-8166; Fax: +81-272-220-8173;

ABSTRACT. The present study was conducted to examine the involvement of the activin-follistatin system in the fibrotic process of the kidney. Immunoreactive activin A was upregulated in tubular cells in the kidneys with unilateral ureteral obstruction but not in normal and contralateral kidneys. Activin A promoted cell proliferation, enhanced the expression of type I collagen mRNA, and induced the production of -smooth muscle actin in a rat kidney fibroblast cell line (NRK-49F cells) as well as in primary cultured renal interstitial fibroblasts. In contrast, activin A did not affect the expressions of -smooth muscle actin and type I collagen in renal epithelial tubular cell lines LLC-PK1, and MDCK. Follistatin, an antagonist of activin A, significantly inhibited cell proliferation in NRK-49F cells. Blockade of activin signaling by overexpression of truncated type II activin receptor, which lacked the intracellular kinase domain, decreased cell proliferation and reduced the expression level of type I collagen mRNA in NRK-49F cells. The expression of activin A was induced by TGF-1 or activin A itself. Induction of type I collagen expression by TGF-1 was reduced by follistatin or by overexpression of truncated type II activin receptor. These results suggest that activin A produced by tubular cells acts as a paracrine factor that activates renal interstitial fibroblasts during the fibrotic processes of the kidney. E-mail: amaeshima@ucsd.edu

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673