Enhanced proliferation and differentiation of ho-1 gene-modified bone marrow-derived mesenchymal stem cells in the acute injured kidney

Abstract

The aim of the present study was to investigate the effect of heme oxygenase-1 (HO-1) overexpression on the survival and differentiation ability of bone marrow-derived mesenchymal stem cells (BMSCs) in the acute kidney injuiy (AKI) microenvironment. HO-l-BMSCs and enhanced green fluorescent protein (eGFP)-BMSCs were constructed. Rat ischemia/reperfusion (I/R)-AKI-kidney homogenate supernatant was prepared to treat the BMSCs. eGFP-BMSCs and HO-l-BMSCs in vitro. In the AKI microenvironment. the HO-l-BMSCs exhibited a smaller proportion of cells at the G0/G1 phase, and a larger proportion of cells expressing proliferating cell nuclear antigen (PCNA) and cytoker- atin 18 (CK18). Phosphorylated protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) protein levels were observed to be increased in the HO-l-BMSCs compared with the BMSCs. LY294002 and PD98059 each inhibited the above effects. BMSCs. eGFP-BMSCs and HO-l-BMSCs were implanted into an L'R-AKI rat model. The proportions of PCNA- BMSCs and CK18- BMSCs were higher in the HO-l-BMSCs group compared with the BMSCs group, which resulted in a decreased acute tubular necrosis score and improved renal function for the AKI rats. In conclusion, the enhanced proliferation and differentiation of HO-l-BMSCs suggest the beneficial effects of such cells in the BMSC-based therapy of AKI. The mechanism underlying these effects may involve the stimulation of Akt and ERK signaling.