Involvement of the activin-follistatin system in tubular regeneration after renal ischemia in rats.
This study was conducted to investigate the involvement of the activin-follistatin system in renal regeneration after ischemic injury. Expression of mRNA for the activin beta(A) subunit was not detected in normal kidneys but increased markedly after renal ischemia. Immunoreactive beta(A) subunit was detected in tubular cells of the outer medulla in ischemic but not normal kidneys. Expression of mRNA for follistatin, an antagonist of activin A, was abundant in tubular cells of the outer medulla in normal kidneys and decreased significantly after renal ischemia. For assessment of the role of the activin-follistatin system in renal regeneration after ischemic injury, recombinant follistatin was intravenously infused into rats with renal ischemia, at the time of reperfusion. Exogenous follistatin prevented the histologic changes induced by ischemic injury, reduced apoptosis in tubular cells, and accelerated tubular cell proliferation. Serum levels of creatinine and blood urea nitrogen were significantly lower in follistatin-treated rats. Conversely, intravenous administration of recombinant activin A inhibited tubular cell proliferation after ischemic injury. These results indicate that the activin-follistatin system participates in renal regeneration after ischemic injury. Follistatin administered intravenously accelerates renal regeneration after renal ischemia, presumably by blocking the actions of endogenous activin.
Maeshima
Akito
A
Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.|Third Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Zhang
You-Qing
YQ
Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
Nojima
Yoshihisa
Y
Third Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Naruse
Takuji
T
Third Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Kojima
Itaru
I
Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
D029404:Activin Receptors; D028341:Activins; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D038681:Follistatin; D006023:Glycoproteins / Q000494:pharmacology / Q000502:physiology*; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007265:Inhibins / Q000494:pharmacology / Q000502:physiology*; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007684:Kidney Tubules / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017978:Receptors, Growth Factor / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012038:Regeneration / Q000502:physiology*; D012079:Renal Circulation
D038681:Follistatin; D006023:Glycoproteins; D006133:Growth Substances; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; D028341:Activins; D007265:Inhibins; D004247:DNA; D029404:Activin Receptors