Bone marrow mesenchymal stem cells repair Cr (Ⅵ)- injured kidney by regulating mitochondria-mediated apoptosis and mitophagy mediated via the MAPK signaling pathway

摘要

The present study aimed to explore the repair effect and mechanism of bone marrow mesenchymal stem cells (BMSCs) transplantation on injured kidneys caused by hexavalent chromium (Cr (VI)). Wistar rats were intraperitoneally injected with 0.4 mg/kg.bw Cr (VI) ion solution. After 30 days, 1 x 10(7) BMSCs were transplanted into rats. After cell transplantation for 2 weeks, there was no significant difference in the chromium content between the model and BMSCs-therapy group by atomic absorption spectrometry. In BMSCs-therapy group, the renal organ index, the serum levels of blood urea nitrogen (BUN) and creatinine (CRE), malonaldehyde (MDA) content were significantly decreased, superoxide dismutase (SOD) activity was significantly elevated, and the pathological changes were improved compared with the model group. The results of immunohistochemical and western blot assays showed that the expressions of apoptosis-related proteins Bax, Cytochrome c, and Caspase-3, as well as autophagy-associated proteins Beclin 1, PINK1, Parkin, p-Parkin, LC3B, and the MAPK signaling pathway, including the ratio of p-p38 to p38 and p-JNK to JNK were all significantly decreased, Bcl-2 and p62 expressions, and the ratio of p-ERK to ERK were significantly elevated in BMSCs-therapy group compared with the model group. These results suggested that BMSCs repaired Cr (VI)-injured kidney through decreasing mitochondria-mediated apoptosis and mitophagy mediated by downregulating phosphorylation of p38 and JNK, upregulating phosphorylation of ERK.