Microvesicles derived from human umbilical cord mesenchymal stem cells ameliorate renal ischemia-reperfusion injury via delivery of miR-21

Autor: Wenxia Chen, Rui-Jin Zhou, Jun Zhou, Jie Liu, Degang Ding, Ling-Dian Wang, Lu Rong, Xiao-li Zhang, Tao Du, Tong-yu Ji
Rok vydání: 2020
Předmět:
Zdroj: Cell Cycle
ISSN: 1551-4005
1538-4101
DOI: 10.1080/15384101.2020.1748940
Popis: Microvesicles (MVs) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs-MVs) and miR-21 were demonstrated to ameliorate renal ischemia-reperfusion injury (IRI). Since hUC-MSC-MVs contained a substantial quantity of miR-21, we speculated that miR-21 might account for a part of the therapeutic effects of hUC-MSCs-MVs. The human tubule epithelial (HK-2) cells were cultured under low oxygen (LO) condition to mimic a cellular IRI model. A rat model of unilateral renal IRI was established. A co-culture model of HK-2 cells and MSC-MVs was utilized to examine the therapeutic role of MSC-MVs in HK-2 cell apoptosis and mechanism. The results showed that hUC-MSCs-MVs inhibited LO-induced HK-2 cell apoptosis through transferring miR-21 to HK-2 cells. Mechanistically, miR-21 directly targeted and negatively regulated programmed cell death protein 4 (PDCD4) in HK-2 cells. Moreover, PDCD4 overexpression in HK-2 cells abrogated the hUC-MSCs-MVs-inhibited HK-2 cell apoptosis under LO condition. Additionally, the beneficial effect of MSC-MVs on rat renal IRI was partly eliminated when miR-21 was knocked down in MSCs. Taken together, MSC-MVs inhibit tubular epithelial cell apoptosis and ameliorate renal IRI, at least partially, via delivery of miR-21.
Databáze: OpenAIRE