Fibroblast growth factor receptor 1 is a key inhibitor of TGFβ signaling in the endothelium

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Sci. Signal.  23 Sep 2014:
Vol. 7, Issue 344, pp. ra90
DOI: 10.1126/scisignal.2005504

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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.

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