Журнал исследований и терапии стволовых клеток

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Mesenchymal Stem Cells Attenuate the Renal Tubular Epithelial Cells Epithelial Mesenchymal Transition by Restoring the Reciprocal Balance between Hepatocyte Growth Factor and Transforming Growth Factor-β1

Junjun Wei, Li Tang, Shuwei Zhang, Liangliang Chen, Zhenhua Xie, Ren Yu, Honggang Qi, Jiangyong Lou and Guobin Weng

Objective: Mesenchymal stem cells (MSCs) have recently shown promise for the treatment of various types of chronic kidney disease models. However, the mechanism of this effect is still not well understood. Our study is aimed to investigate the effect of MSCs on transforming growth factor-β1 (TGF-β1)-induced EMT in renal tubular epithelial cells (HK-2 cells) and the underlying mechanism related to the reciprocal balance between hepatocyte growth factor (HGF) and TGF-β1.
Methods: HK-2 cells were treated with TGF-β1-then co-cultured with MSCs. The induced EMT was assessed by cellular morphology and the expressions of alpha-smooth muscle actin (α-SMA) and EMT-related proteins. MTT assay and flow cytometry were employed to detect the effect of TGF-β1 and MSCs on HK-2 cell proliferation and apoptosis. SiRNA against hepatocyte growth factor (siHGF) was transfected to decrease the expression of HGF to identify the role of HGF in MSCs inhibiting HK-2 EMT.
Results: TGF-β1 decreased HGF expression, induced EMT, suppressed proliferation and promoted apoptosis in HK-2 cells; but when co-cultured with MSCs all the outcomes were reversed. However, after treated with siHGF, all the benefits taken from MSCs vanished.
Conclusion: TGF-β1 was a motivating factor of renal cell EMT and it suppressed the HGF expression. However, MSCs provided protection against EMT by increasing HGF level and decreasing TGF-β1 level. Our results also demonstrated HGF is one of the critical factor in MSCs anti-fibrosis.