Resveratrol improves human umbilical cord-derived mesenchymal stem cells repair for cisplatin-induced acute kidney injury.

Abstract

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 μmol/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.

• Authors: Rongxue Zhang, Lei Yin, Bin Zhang, Hui Shi, Yaoxiang Sun, Cheng Ji, Jingyan Chen, Peipei Wu, Leilei Zhang, Wenrong Xu, Hui Qian
• Journal: Cell death & disease (Cell Death Dis) Vol. 9 Issue 10 Pg. 965 (09 20 2018) ISSN: 2041-4889 [Electronic] England
• PMID: 30237401 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cisplatin
• Resveratrol

Topics

• Acute Kidney Injury (chemically induced, drug therapy, metabolism)
• Animals
• Cell Line
• Cell Movement (drug effects)
• Cisplatin (adverse effects)
• Female
• Fluorescent Antibody Technique
• Humans
• In Situ Nick-End Labeling
• Mesenchymal Stem Cells (cytology, drug effects)
• Rats
• Rats, Sprague-Dawley
• Resveratrol (therapeutic use)
• Signal Transduction (drug effects)
• Umbilical Cord (cytology)