3162

HMOX1

epithelialmesenchymal transition (EMT) is a key mechanism underlying metastatic breast cancer. Reactive oxygen species (ROS) play an important role in EMT. Heme oxygenase1 (HMOX1) can reduce oxidative stress. However, the effect of HMOX1 on the EMT process in breast cancer cells is unknown. We treated the MCF7 breast cancer cell line with the HMOX1 inducer hemin and observed that hemin induced HMOX1 expression and inhibited migration, invasion and ROS generation in transforming growth factorbeta (TGFbeta)treated MCF7 cells using quantitative RTqPCR, western blotting, woundhealing and cell invasion assays as well as fluorescent probe DCFDA. Hemin inhibited TGFbetainduced EMT in the MCF7 cells, whereas HMOX1 siRNA attenuated the suppressive effect of hemin as determined by the expression and cellular distribution of selected EMT markers. In summary, our results revealed that hemin treatment increased HMOX1 expression and inhibited TGFbetainduced EMT in MCF7 cells.

Induction of heme oxygenase-1 (HO-1) is associated with potential antifibrogenic effects. The effects of HO-1 expression on epithelial-mesenchymal transition (EMT), which plays a critical role in the development of renal fibrosis, are unknown. In this study, HO-1(-/-) mice demonstrated significantly more fibrosis after 7 d of unilateral ureteral obstruction compared with wild-type mice, despite similar degrees of hydronephrosis. The obstructed kidneys of HO-1(-/-) mice also had greater macrophage infiltration and renal tubular TGF-beta1 expression than wild-type mice. In addition, the degree of EMT was more extensive in obstructed HO-1(-/-) kidneys, as assessed by alpha-smooth muscle actin and expression of S100A4 in proximal tubular epithelial cells. In vitro studies using proximal tubular cells isolated from HO-1(-/-) and wild-type kidneys confirmed these observations. In conclusion, HO-1 deficiency is associated with increased fibrosis, tubular TGF-beta1 expression, inflammation, and enhanced EMT in obstructive kidney disease. Modulation of the HO-1 pathway may provide a new therapeutic approach to progressive renal diseases.

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 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 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.