Polydatin ameliorates renal ischemia/reperfusion injury by decreasing apoptosis and oxidative stress through activating sonic hedgehog signaling pathway |
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| Affiliation: | 1. Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi''an 710032, Shaanxi, China;2. Department of Natural Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi''an 710032, Shaanxi, China;3. State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi''an 710032, Shaanxi, China;1. Dipartimento di Matematica, Università della Calabria, via P. Bucci 30/B, Arcavacata di Rende I-87036, Cosenza, Italy;2. INFN, Gruppo Collegato di Cosenza, Arcavacata di Rende I-87036, Cosenza, Italy;3. IAC, Consiglio Nazionale delle Ricerche, via dei Taurini, 19, I-00185, Roma, Italy;4. IAC, Sez. di Napoli, Consiglio Nazionale delle Ricerche, via P. Castellino 111, I-80131, Napoli, Italy;1. Infectious Disease Division, Winthrop-University Hospital, Mineola, NY, USA;2. State University of New York, School of Medicine, Stony Brook, NY, USA;1. The Ioffe Institute, 26, Polytekhnicheskaya st, St. Petersburg, 194021, Russia;2. ITMO University, 49, Kronverksky ave., St. Petersburg, 197101, Russia;1. Department of Rehabilitation, Yantai Yuhuangding Hospital, Yantai, China;2. Department of Cardiology, Yantai Yuhuangding Hospital, Yantai, China;3. Department of Hospital Preparation Center, Yantai Yuhuangding Hospital, Yantai, China;4. Department of Trauma Orthopedic, Yantai Yuhuangding Hospital, Yantai, China;5. Department of Imaging, Yantai Yuhuangding Hospital, Yantai, China |
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| Abstract: | Polydatin, a glucoside of resveratrol, recently has been demonstrated possibly to exert its biological effects by targeting sonic hedgehog (Shh). However, whether Shh signaling pathway is involved in the therapeutic effects of polydatin for renal ischemia/reperfusion (I/R) injury has not been evaluated. Our results showed that I/R induced the secretion of Shh, upregulated Patched and Smoothened, and enhanced the nuclear translocation and target gene transcription of Glioblastoma 1 in renal I/R injury models, which were further upregulated after the administration of polydatin significantly and in turn exerted prominent nephroprotective effects against cell apoptosis and oxidative stress. The treatment with cyclopamine (a specific inhibitor of Smoothened) or 5E1 (an anti-Shh antibody) not only markedly inhibited the activation of the Shh pathway, but also dramatically suppressed the nephroprotective effects of polydatin above-mentioned. These results advance our knowledge that polydatin can provide protection for kidneys against I/R injury by enhancing antioxidant capacity and decreasing cell apoptosis through activating Shh signaling pathway. |
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| Keywords: | Polydatin Ischemia Kidney Hedgehog Apoptosis Oxidative stress |
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