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)

Glial cell line-derived neurotrophic growth factor (GDNF), a member of the transforming growth factor family, is necessary for renal organogenesis and exhibits changes in expression in models of renal disease. Nestin is an intermediate filament protein originally believed to be a marker of neuroepithelial stem cells and recently proposed as a marker of mesenchymal stem cells (MSC). Having demonstrated the participation of nestin-expressing cells in renoprotection during acute renal ischemia, we hypothesized that growth factors and transcription factors similar to those operating in the nervous system should be also operant in the kidney and may be induced after noxious stimuli, such as an ischemic episode. Using cultured kidney-derived MSC, which abundantly express nestin, we confirmed expression of GDNF by these cells and demonstrated the GDNF-induced expression of GDNF. The cellular expression of nestin paralleled that of GDNF: serum starvation decreased the expression, whereas application of GDNF resulted in a dose-dependent increase in nestin expression. Immunohistochemical and Western blot analyses of kidneys obtained from control and postischemic mice showed that expression of GDNF was much enhanced in the renal cortex, a pattern similar to the previously reported expression of nestin. Based on the observed GDNF-induced GDNF expression, we next explored the effect of supplemental GDNF administered early after ischemia on renal function postischemia. GDNF-treated mice were protected against acute ischemia. To address potential mechanisms of the observed renoprotection, in vitro studies showed that GDNF accelerated MSC migration in a wound-healing assay. Hypoxia did not accelerate, but rather slightly reduced, the motility of MSC and reduced the expression of GDNF in MSC by approximately twofold. Furthermore, GDNF was cytoprotective against oxidative stress-induced apoptotic death of MSC. Collectively, these data establish 1) an autoregulatory circuit of GDNF-induced GDNF expression in renal MSC; 2) induction of GDNF expression in postischemic kidneys; 3) the ability of exogenous GDNF to ameliorate ischemic renal injury; and 4) a possible contribution of GDNF-induced motility and improved survival of MSC to renoprotection.
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PMID:Glial cell line-derived neurotrophic growth factor increases motility and survival of cultured mesenchymal stem cells and ameliorates acute kidney injury. 1800 56

Adult kidney stem cells are known to have important roles in renal regeneration after acute kidney injury. Although trophic factors from tissue stem cells have been reported to promote the regeneration of other organs, there is limited number of evidence of this phenomenon in the kidneys. Here, we explored the effects of secreted factors from kidney stem cells. We intraperitoneally administered culture supernatant obtained from adult rat kidney stem/progenitor cells into rat kidney ischemia/reperfusion injury models, and the treatment significantly ameliorated renal tubulointerstitial injury, suppressed tubular cell apoptosis, diminished inflammation and promoted the proliferation of both residual renal cells and immature cells. In vitro, treatment with culture supernatant from kidney stem cells significantly promoted cell proliferation and suppressed cisplatin-induced cell apoptosis in both normal rat kidney cells and kidney stem cells. In addition, treatment with culture supernatant increased the expression of nestin in normal rat kidney cells, suggesting the dedifferentiation of tubular cells into stem-like cells. Analysis of the culture supernatant revealed that it contained a variety of growth factors. Taken together, the results suggest that these factors together lead to renal regeneration. In conclusion, adult kidney stem cells contribute to renal regeneration indirectly through the secretion of regenerative factors.
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PMID:Adult kidney stem/progenitor cells contribute to regeneration through the secretion of trophic factors. 3250 97