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Exosomes from human‐bone‐marrow‐derived mesenchymal stem cells protect against renal ischemia/reperfusion injury via transferring miR‐199a‐3p
Author(s) -
Zhu Gongmin,
Pei Lijiao,
Lin Fan,
Yin Hubin,
Li Xinyuan,
He Weiyang,
Liu Nian,
Gou Xin
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28941
Subject(s) - mesenchymal stem cell , protein kinase b , mapk/erk pathway , microvesicles , cancer research , pi3k/akt/mtor pathway , microbiology and biotechnology , gene knockdown , stem cell , signal transduction , medicine , chemistry , apoptosis , biology , microrna , biochemistry , gene
Renal ischemia/reperfusion (I/R) injury is the main reason for acute kidney injury (AKI) and is closely related to high morbidity and mortality. In this study, we found that exosomes from human‐bone‐marrow‐derived mesenchymal stem cells (hBMSC‐Exos) play a protective role in hypoxia/reoxygenation (H/R) injury. hBMSC‐Exos were enriched in miR‐199a‐3p, and hBMSC‐Exo treatment increased the expression level of miR‐199a‐3p in renal cells. We further explored the function of miR‐199a‐3p on H/R injury. miR‐199a‐3p was knocked down in hBMSCs with a miR‐199a‐3p inhibitor. HK‐2 cells cocultured with miR‐199a‐3p‐knockdown hBMSCs were more susceptible to H/R injury and showed more apoptosis than those cocultured with hBMSCs or miR‐199a‐3p‐overexpressing hBMSCs. Meanwhile, we found that HK‐2 cells exposed to H/R treatment incubated with hBMSC‐Exos decreased semaphorin 3A (Sema3A) and activated the protein kinase B (AKT) and extracellular‐signal‐regulated kinase (ERK) pathways. However, HK‐2 cells cocultured with miR‐199a‐3p‐knockdown hBMSCs restored Sema3A expression and blocked the activation of the AKT and ERK pathways. Moreover, knocking down Sema3A could reactivate the AKT and ERK pathways suppressed by a miR‐199a‐3p inhibitor. In vivo, we injected hBMSC‐Exos into mice suffering from I/R injury; this treatment induced functional recovery and histologic protection and reduced cleaved caspase‐3 and Sema3A expression levels, as shown by immunohistochemistry. On the whole, this study demonstrated an antiapoptotic effect of hBMSC‐Exos, which protected against I/R injury, via delivering miR‐199a‐3p to renal cells, downregulating Sema3A expression and thereby activating the AKT and ERK pathways. These findings reveal a novel mechanism of AKI treated with hBMSC‐Exos and provide a therapeutic method for kidney diseases.