Chen Pei-Yu, Qin Lingfeng, Tellides George, Simons Michael
Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Department of Surgery, Yale University School of Medicine, New Haven, CT 06520, USA.
Sci Signal. 2014 Sep 23;7(344):ra90. doi: 10.1126/scisignal.2005504.
Abnormal vascular homeostasis can lead to increased proliferation of smooth muscle cells and deposition of extracellular matrix, resulting in neointima formation, which contributes to vascular lumen narrowing, a pathology that underlies diseases including transplant vasculopathy, the recurrence of stenosis, and atherosclerosis. Growth of neointima is in part due to endothelial-to-mesenchymal transition (EndMT), a transforming growth factor-β (TGFβ)-driven process, which leads to increased numbers of smooth muscle cells and fibroblasts and deposition of extracellular matrix. We reported that endothelial cell-specific knockout of fibroblast growth factor receptor 1 (FGFR1) led to activation of TGFβ signaling and development of EndMT in vitro and in vivo. Furthermore, EndMT in human diseased vasculature correlated with decreased abundance of FGFR1. These findings identify FGFR1 as the key regulator of TGFβ signaling and EndMT development.
异常的血管稳态可导致平滑肌细胞增殖增加和细胞外基质沉积，从而形成新生内膜，这会导致血管腔狭窄，这种病理状态是包括移植血管病变、狭窄复发和动脉粥样硬化等疾病的基础。新生内膜的生长部分归因于内皮-间充质转化（EndMT），这是一个由转化生长因子-β（TGFβ）驱动的过程，会导致平滑肌细胞和成纤维细胞数量增加以及细胞外基质沉积。我们报道，内皮细胞特异性敲除成纤维细胞生长因子受体1（FGFR1）会导致TGFβ信号激活以及体内外EndMT的发展。此外，人类病变血管中的EndMT与FGFR1丰度降低相关。这些发现确定FGFR1是TGFβ信号和EndMT发展的关键调节因子。
