肝细胞生长因子通过下调 Notch 信号减轻 TGF-β1 诱导的 EndMT 的发生。
Hepatocyte Growth Factor Attenuates the Development of TGF-β1- Induced EndMT through Down-regulating the Notch Signaling.
机构信息
Department of Emergency Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China.
The Center of Health Management, West China Medical Center, Chengdu, Sichuan, 610000, China.
出版信息
Endocr Metab Immune Disord Drug Targets. 2020;20(5):781-787. doi: 10.2174/1871530319666191023141638.
BACKGROUND AND OBJECTIVE
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
背景与目的
内皮-间充质转化（EndMT）不仅发生在胚胎发育过程中，而且还与心血管疾病、纤维化甚至癌症等多种疾病有关。然而，其具体的分子生物学机制及相关通路之间的关系尚未完全阐明。本研究旨在探讨 HGF 对 EndMT 的抑制作用及 Notch 信号在此过程中的分子机制。
方法
用 TGF-β1 和/或 HGF 处理 HUVECs 72 小时。通过 qRT-PCR 和 Western blot 检测 EndMT 标志物和 Notch 信号通路关键转录因子的表达水平。通过 qRT-PCR 检测 C-Met 的表达。
结果
TGF-β1 诱导的 EndMT 过程中 CD31 下调，α-SMA、FSP1 上调。HGF 处理通过下调 Notch 信号通路的信号转导，显著抑制 TGF-β1 诱导的 EndMT 的发展。
结论
本研究证明 HGF 处理通过抑制 Notch 信号显著抑制 TGF-β1 诱导的 EndMT 的发展，这可能为治疗血管疾病和由 EndMT 引起的多种纤维化疾病提供新的理论基础。
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