Enhanced proliferation and differentiation of HO-1 gene-modified bone marrow-derived mesenchymal stem cells in the acute injured kidney.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 injury (AKI) microenvironment.  HO-1-BMSCs and enhanced green fluorescent protein (eGFP)-BMSCs were constructed.  Rat ischemia/reperfusion (I/R)‑AKI-kidney homogenate supernatant was prep-ared to treat the BMSCs, eGFP-BMSCs and HO-1-BMSCs in vitro.  In the AKI microenvironment, the HO-1-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 cytokeratin 18 (CK18).  Phosphorylated protein kinase B (Akt) and extracellular signal‑regulated kinase (ERK) protein levels were observed to be increased in the HO-1-BMSCs compared with the BMSCs.  LY294002 and PD98059 each inhibited the above effects.  BMSCs, eGFP-BMSCs and HO-1-BMSCs were implanted into an I/R-AKI rat model.  The proportions of PCNA+ BMSCs and CK18+ BMSCs were higher in the HO-1-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-1-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.
C