PMID- 30237401 OWN - NLM STAT- MEDLINE DCOM- 20191125 LR - 20191125 IS - 2041-4889 (Electronic) VI - 9 IP - 10 DP - 2018 Sep 20 TI - Resveratrol improves human umbilical cord-derived mesenchymal stem cells repair for cisplatin-induced acute kidney injury. PG - 965 LID - 10.1038/s41419-018-0959-1 [doi] LID - 965 AB - Human umbilical cord-derived mesenchymal stem cells (hucMSCs) are a promising tool for damaged tissues repair, especially for the kidney. However, their efficacy requires improvement. In order to optimize the clinical utility of hucMSCs, we adopted a strategy of treating hucMSCs with 20 mumol/L of resveratrol (Res-hucMSCs), applying it in a cisplatin-induced acute kidney injury model. Interestingly, we found that Res-hucMSCs exhibited a more efficient repairing effect than did hucMSCs. Resveratrol-promoted hucMSCs secreted platelet-derived growth factor-DD (PDGF-DD) into renal tubular cells resulting in downstream phosphorylation of extracellular signal-regulated kinase (ERK), which inhibited renal tubular cells apoptosis. In contrast, PDGF-DD knockdown impaired the renal protection of Res-hucMSCs. In addition, angiogenesis induced by PDGF-DD in endothelial cells was also involved in the renal protection of Res-hucMSCs. The conditioned medium of Res-hucMSCs accelerated proliferation and migration of vascular endothelial cells in vitro and CD31 was in a high-level expression in Res-hucMSCs group in vivo. Nevertheless, the angiogenesis was abrogated when Res-hucMSCs were treated with PDGF-DD siRNA. In conclusion, our findings showed that resveratrol-modified hucMSCs activated ERK pathway in renal tubular cells and promoted angiogenesis in endothelial cells via paracrine PDGF-DD, which could be a novel strategy for enhancing the therapy efficacy of hucMSCs in cisplatin-induced kidney injury. FAU - Zhang, Rongxue AU - Zhang R AD - Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China. AD - Huai'an maternity and child health care hospital, Huai'an, Jiangsu, People's Republic of China. FAU - Yin, Lei AU - Yin L AD - Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China. FAU - Zhang, Bin AU - Zhang B AD - Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China. FAU - Shi, Hui AU - Shi H AD - Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China. FAU - Sun, Yaoxiang AU - Sun Y AD - Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China. FAU - Ji, Cheng AU - Ji C AD - Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China. FAU - Chen, Jingyan AU - Chen J AD - Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China. FAU - Wu, Peipei AU - Wu P AD - Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China. FAU - Zhang, Leilei AU - Zhang L AD - Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China. FAU - Xu, Wenrong AU - Xu W AD - Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China. icls@ujs.edu.cn. FAU - Qian, Hui AU - Qian H AD - Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China. lstmmmlst@163.com. AD - Key Laboratory of Embryo Molecular Biology, Ministry of Health and Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai, People's Republic of China. lstmmmlst@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180920 PL - England TA - Cell Death Dis JT - Cell death & disease JID - 101524092 RN - Q20Q21Q62J (Cisplatin) RN - Q369O8926L (Resveratrol) SB - IM MH - Acute Kidney Injury/*chemically induced/*drug therapy/metabolism MH - Animals MH - Cell Line MH - Cell Movement/drug effects MH - Cisplatin/*adverse effects MH - Female MH - Fluorescent Antibody Technique MH - Humans MH - In Situ Nick-End Labeling MH - Mesenchymal Stem Cells/*cytology/*drug effects MH - Rats MH - Rats, Sprague-Dawley MH - Resveratrol/*therapeutic use MH - Signal Transduction/drug effects MH - Umbilical Cord/*cytology PMC - PMC6148224 COIS- The authors declare that they have no conflict of interest. EDAT- 2018/09/22 06:00 MHDA- 2019/11/26 06:00 PMCR- 2018/09/20 CRDT- 2018/09/22 06:00 PHST- 2018/03/21 00:00 [received] PHST- 2018/08/01 00:00 [accepted] PHST- 2018/07/06 00:00 [revised] PHST- 2018/09/22 06:00 [entrez] PHST- 2018/09/22 06:00 [pubmed] PHST- 2019/11/26 06:00 [medline] PHST- 2018/09/20 00:00 [pmc-release] AID - 10.1038/s41419-018-0959-1 [pii] AID - 959 [pii] AID - 10.1038/s41419-018-0959-1 [doi] PST - epublish SO - Cell Death Dis. 2018 Sep 20;9(10):965. doi: 10.1038/s41419-018-0959-1.