Exogenous MSCs ameliorate hypoxia/reoxygenation injury in renal tubular epithelial cells through JAK/STAT signaling pathway-mediated regulation of HMGB1.

This study was conducted to investigate the repair mechanism of hypoxia/reoxygenation injury (HRI) in renal tubular epithelial cells (HK-2) by exogenous mesenchymal stem cells (MSCs). The activation of the JAK/STAT pathway in HK-2 cells after HRI and treatment of MSCs, JAK inhibitor WP1066 and STAT inhibitor SOCS3 was investigated using Western blot analysis. HK-2 cells were transfected with siRNA STAT3 and analyzed for expression of STAT3, JAK2 and HMGB1 using fluorescence quantitative PCR and Western blot. Cell viability and apoptosis were analyzed using the MTT assay and flow cytometry. After HRI, the JAK/STAT pathway in HK-2 cells was activated, resulting in the upregulation of JAK1, JAK2, JAK3, p-JAK1, p-JAK2, p-JAK3, STAT1, STAT2, STAT3, p-STAT1, p-STAT2 and p-STAT3. After treatment with MSC conditioned medium (MSCs CM), WP1066, or SOCS, the expression of these proteins was significantly down-regulated. When the cells were transfected with siRNA STAT3, the expression of STAT3 at protein and mRNA levels and JAK2 and HMGB1 at mRNA level was down-regulated; the cell viability was reduced and apoptosis increased. It is concluded that exogenous MSCs reduce HRI of HK-2 cells by suppressing the JAK/STAT signaling pathway and down-regulating the expression of HMGB1.