Activin A is a potent activator of renal interstitial fibroblasts.
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 alpha-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 alpha-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-beta 1 or activin A itself. Induction of type I collagen expression by TGF-beta 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.
Yamashita
Shin
S
Third Department of Internal Medicine, Gunma University School of Medicine,Showa, Maebashi, Japan.
Maeshima
Akito
A
Kojima
Itaru
I
Nojima
Yoshihisa
Y
D028341:Activins / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002455:Cell Division; D005347:Fibroblasts / Q000502:physiology*; D005355:Fibrosis; D028322:Inhibin-beta Subunits / Q000235:genetics / Q000502:physiology*; D007668:Kidney / Q000473:pathology*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014517:Ureteral Obstruction / Q000473:pathology
D012333:RNA, Messenger; C422405:activin A; D028341:Activins; D028322:Inhibin-beta Subunits