Mesenchymal stem cells-microvesicle-miR-451a ameliorate early diabetic kidney injury by negative regulation of P15 and P19.

Mesenchymal stem cells-microvesicle-miR-451a ameliorate early diabetic kidney injury by negative regulation of P15 and P19.

Exp Biol Med (Maywood). 2019 Jan 06;:1535370218819726

Authors: Zhong L, Liao G, Wang X, Li L, Zhang J, Chen Y, Liu J, Liu S, Wei L, Zhang W, Lu Y

Abstract
IMPACT STATEMENT: The mechanism of MSCs repairing the injured kidney in diabetic nephropathy is not yet clear. In the research, MVs showed the same surface markers as MSCs but much higher MiR-451a expression. miR-451a was decreased in both injured HK-2 cells and kidneys. MV-miR-451a stimulated the cell proliferation and viability in vitro and promoted structural and functional improvements of injured kidney in vivo. Infusion of MV-miR-451a ameliorated EMT by reducing α-SMA and increasing E-cadherin. These effects relied on the improved cell cycle arrest and the down-regulation of P15 and P19 via miR-451a binding to their 3'-UTR region. This study demonstrated that MSC-MV-miR-451a could specifically inhibit cell cycle inhibitors to restart the blocked cell cycle and reverse EMT in vivo and in vitro. Therefore, miR-451a may be a new target for DN therapy.

PMID: 30614256 [PubMed - as supplied by publisher]

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