Inhibition of mTORC1 signaling protects kidney from irradiation-induced toxicity via accelerating recovery of renal stem-like cells

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Date: Aug. 14, 2018
From: Stem Cell Research & Therapy(Vol. 9, Issue 1)
Publisher: BioMed Central Ltd.
Document Type: Report
Length: 6,589 words
Lexile Measure: 1370L

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Abstract :

Background Irradiation-induced kidney damage is inevitable during radiotherapeutic practice, which limits effective radiotherapy doses on tumor treatment. In the present study, the role of mTOR complex 1 (mTORC1) signaling was investigated in irradiation-induced renal injuries. Methods Mice were exposed to 8.0-Gy X-ray of total body irradiation and subsequently treated with rapamycin. Changes of renal morphology were assessed by hematoxylin and eosin staining. Expression of pS6 and CD133 was detected via immunostaining. Cellular apoptosis and proliferation were measured by TUNEL, caspase-3 and BrdU staining. Activation of mTORC1, TGF-[beta] and NF-κB signaling pathways was determined through western blot analysis. Results Our data displayed that irradiation disrupted the structures of renal corpuscles and tubules and decreased the density of CD133.sup.+ renal stem-like cells, which were related with increasing cellular apoptosis and decreasing cell proliferation post exposure. Activation of mTORC1, TGF-[beta] and NF-κB signaling pathways was determined in irradiated renal tissues, which were inhibited by rapamycin treatment. Application of rapamycin after irradiation decreased cellular apoptosis and increased autophagy and cell proliferation in renal tissues. The density of CD133.sup.+ renal stem-like cells was significantly increased in irradiated kidneys after rapamycin treatment. The morphology of irradiated renal corpuscles and tubules was gradually recovered upon rapamycin treatment. Conclusions These findings indicate that inhibition of mTORC1 signaling by rapamycin ameliorates irradiation-induced renal toxicity mediated by decreasing cellular apoptosis and increasing CD133.sup.+ renal stem-like cells. Keywords: Irradiation, Renal damage, mTOR complex 1, Rapamycin, Apoptosis

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Gale Document Number: GALE|A556997454