title: Follistatin, an activin antagonist, ameliorates renal interstitial fibrosis in a rat model of unilateral ureteral obstruction.
abstract: Activin, a member of the TGF-β superfamily, regulates cell growth and differentiation in various cell types. Activin A acts as a negative regulator of renal development as well as tubular regeneration after renal injury. However, it remains unknown whether activin A is involved in renal fibrosis. To clarify this issue, we utilized a rat model of unilateral ureteral obstruction (UUO). The expression of activin A was significantly increased in the UUO kidneys compared to that in contralateral kidneys. Activin A was detected in glomerular mesangial cells and interstitial fibroblasts in normal kidneys. In UUO kidneys, activin A was abundantly expressed by interstitial α-SMA-positive myofibroblasts. Administration of recombinant follistatin, an activin antagonist, reduced the fibrotic area in the UUO kidneys. The number of proliferating cells in the interstitium, but not in the tubules, was significantly lower in the follistatin-treated kidneys. Expression of α-SMA, deposition of type I collagen and fibronectin, and CD68-positive macrophage infiltration were significantly suppressed in the follistatin-treated kidneys. These data suggest that activin A produced by interstitial fibroblasts acts as a potent profibrotic factor during renal fibrosis. Blockade of activin A action may be a novel approach for the prevention of renal fibrosis progression.
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Maeshima
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Mishima
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Yamashita
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Masao
authors.identifier: 0000-0002-8612-8915
authors.initials: M
authors.lastname: Nakasatomi
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miya
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sakurai
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Sakairi
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Hidekazu
authors.identifier: 0000-0002-0768-7090
authors.initials: H
authors.lastname: Ikeuchi
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Keiju
authors.initials: K
authors.lastname: Hiromura
authors.affiliation: School of Veterinary Medicine and Animal Science, Kitasato University, Towada 034-8628, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Kojima
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nojima
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D005355:Fibrosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D038681:Follistatin / Q000008:administration & dosage*; D006801:Humans; D028322:Inhibin-beta Subunits / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D016212:Transforming Growth Factor beta / Q000235:genetics; D014517:Ureteral Obstruction / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D038681:Follistatin; D016212:Transforming Growth Factor beta; C103008:inhibin beta A subunit; D028322:Inhibin-beta Subunits