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

Liu,Nanmei; Wang,Huiling; Han,Guofeng; Cheng,Jin; Hu,Weifeng; Zhang,Jinyuan

doi:10.3892/ijmm.2018.3670

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

Authors:
- Nanmei Liu
- Huiling Wang
- Guofeng Han
- Jin Cheng
- Weifeng Hu
- Jinyuan Zhang
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Affiliations: Department of Nephrology, The 455th Hospital of PLA, Shanghai 200052, P.R. China
Published online on: May 11, 2018 https://doi.org/10.3892/ijmm.2018.3670
Pages: 946-956
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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 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 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.

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