Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0920646 (renal ischemia)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Involvement of the activin-follistatin system in tubular regeneration after renal ischemia in rats. 1146 41

It has been recently shown that in ischemic rat kidneys activin A is induced in tubular cells and inhibits their regeneration. The present study was conducted to further investigate the action of activin A in tubular cells during regeneration. Among genes thought to be critical for kidney development, Pax-2 was upregulated in tubular cells during regeneration after renal ischemia. Pax-2 protein was localized in nuclei of tubular and interstitial cells, some of which co-expressed a mesenchymal cell marker, vimentin, suggesting that a population of Pax-2-positive cells have properties of immature progenitor-like tubular cells. The Pax-2-expressing cells co-expressed a cell proliferation marker, BrdU, activin A, and the type II activin receptor. Activin A modulated growth of BrdU/Pax-2 double-positive cells since an administration of follistatin increased; conversely, exogenous activin A decreased the number of BrdU/Pax-2 double-positive cells after renal ischemia. Activin A also reduced the expression of Pax-2 in cultured metanephroi. A proximal tubular cell line, LLC-PK(1) cells, was used to further study the mode of action of activin A. The expression of Pax-2 was not detected in quiescent LLC-PK(1) cells, but it was markedly increased when growth was stimulated. Under this condition, activin A significantly inhibited DNA synthesis and reduced the expression of Pax-2 in LLC-PK(1) cells. In contrast, blockade of the activin signaling by overexpressing dominantly negative mutant receptor enhanced the expression level of Pax-2 in LLC-PK(1) cells and induced an immature phenotype. These results suggest that activin A regulates tubular cell growth and differentiation by modulating the expression of Pax-2 during regeneration.
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PMID:Involvement of Pax-2 in the action of activin A on tubular cell regeneration. 1244 3