Hepatocyte Growth Factor Attenuates the Development of TGF-β1- Induced EndMT through Down-regulating the Notch Signaling.

Abstract

Endothelial-mesenchymal transition (EndMT) not only occurs during embryonic development, but also contributes to various diseases including cardiovascular diseases, fibrosis, and even cancer. However, the specific molecular biological mechanism and relationship of related pathways have not been fully elucidated. This study aims to explore the inhibitory effect of HGF on EndMT and the molecular mechanism of Notch signal in this process. HUVECs were treated with TGF-β1 and/or HGF for 72 hours. Expression levels of EndMT markers and the key transcriptional regulators of Notch signaling pathway were assessed by qRT-PCR and western blotting. C-Met expression was measured by qRT-PCR. CD31 was downregulated and α-SMA, FSP1 were upregulated during TGF-β1-induced EndMT. HGF treatment significantly attenuates the development of TGF-β1-induced EndMT by down-regulating the signal transduction of the Notch signal pathway. This study proves that HGF treatment significantly attenuates the development of TGF- β1-induced EndMT by inhibiting the Notch signaling, which may provide new theoretical basis for the treatment of vascular diseases and numerous fibrotic diseases caused by EndMT.