02 January 2018 : Original article
Antifibrotic Effects of Hepatocyte Growth Factor on Endothelial-to-Mesenchymal Transition via Transforming Growth Factor-Beta1 (TGF-β1)/Smad and Akt/mTOR/P70S6K Signaling PathwaysZijie Wang1ABCD, Shuang Fei1BCD, Chuanjian Suo1CD, Zhijian Han1D, Jun Tao1C, Zhen Xu1C, Chunchun Zhao1D, Ruoyun Tan1C, Min Gu1AFG*
Ann Transplant 2018; 23:1-10
BACKGROUND: The related mechanisms involved in allograft interstitial fibrosis and chronic allograft dysfunction (CAD), following renal transplant, remain largely unknown. Here, we explored the role of hepatocyte growth factor (HGF) treatment on the endothelial-to-mesenchymal transition (EndMT) as a new way to target and prevent kidney fibrosis and improve outcomes for renal transplant recipients.
MATERIAL AND METHODS: We extracted proteins and mRNAs from human umbilical vein endothelial cells (HUVECs) and human renal glomerular endothelial cells (HRGECs) treated with transforming growth factor-beta1 (TGF-β1) and/or varying doses of HGF, and assessed the effect of HGF on the EndMT using western blotting, qRT-PCR, and ELISA assays. We utilized cell motility and migration assays to evaluate cell movement, and applied western blotting to assess the mechanism by which TGF-β1 induced the EndMT.
RESULTS: HGF significantly attenuated the development of TGF-β1-induced EndMT in a concentration-dependent way, and weakened the abilities of motility and migration of both HUVECs and HRGECs. Moreover, our results reveal that the antifibrotic effect of HGF on the EndMT was associated with the TGF-β/Smad and Akt/mTOR/p70S6K signaling pathways.
CONCLUSIONS: Our study suggests that HGF treatment significantly attenuates the development of EndMT induced by TGF-β1 via the TGFb/Smad and Akt/mTOR/P70S6K signaling, which provides novel insights into the prevention and treatment of interstitial fibrosis and CAD following renal transplant.
Keywords: Hepatocyte Growth Factor, Kidney Transplantation, Renal Insufficiency, Chronic
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Ann Transplant In Press; DOI: 10.12659/AOT.942767
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