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 marrowderived 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 prepared 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 signalregulated 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.
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Document Type: Research Article
Affiliations: Department of Nephrology, The 455th Hospital of PLA, Shanghai 200052, P.R. China
Publication date: January 1, 2018
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- The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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