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: Akito Maeshima, Keiichiro Mishima, Shin Yamashita, Masao Nakasatomi, Masaaki Miya, Noriyuki Sakurai, Toru Sakairi, Hidekazu Ikeuchi, Keiju Hiromura, Yoshihisa Hasegawa, Itaru Kojima, Yoshihisa Nojima
• Journal: BioMed research international (Biomed Res Int) Vol. 2014 Pg. 376191 ( 2014) ISSN: 2314-6141 [Electronic] United States
• PMID: 24883308 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Follistatin
• Transforming Growth Factor beta
• inhibin beta A subunit
• Inhibin-beta Subunits

Topics

• Animals
• Cell Proliferation (drug effects)
• Fibrosis (drug therapy, genetics, pathology)
• Follistatin (administration & dosage)
• Humans
• Inhibin-beta Subunits (antagonists & inhibitors, biosynthesis, metabolism)
• Kidney (drug effects, metabolism, pathology)
• Mesangial Cells (drug effects, metabolism)
• Rats
• Transforming Growth Factor beta (genetics)
• Ureteral Obstruction (drug therapy, genetics, pathology)