FGF Regulates TGF-β Signaling and Endothelial-to-Mesenchymal Transition via Control of let-7 miRNA Expression
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Chen-2012-FGF Regulates TGF-ß.pdf
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Author(s)
Chen, Pei-Yu
Qin, Lingfeng
Barnes, Carmen
Charisse, Klaus
Yi, Tai
Zhang, Xinbo
Ali, Rahmat
Medina, Pedro P.
Yu, Jun
Slack, Frank J.
Date Issued
November 2012
Journal
Cell Reports
Publisher
Elsevier
Citation
Chen, Pei-Yu, Lingfeng Qin, Carmen Barnes, Klaus Charisse, Tai Yi, Xinbo Zhang, Rahmat Ali, et al. “FGF Regulates TGF-β Signaling and Endothelial-to-Mesenchymal Transition via Control of Let-7 miRNA Expression.” Cell Reports 2, no. 6 (December 2012): 1684–1696.
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Final published version
Abstract
Maintenance of normal endothelial function is critical to various aspects of blood vessel function, but its regulation is poorly understood. In this study, we show that disruption of baseline fibroblast growth factor (FGF) signaling to the endothelium leads to a dramatic reduction in let-7 miRNA levels that, in turn, increases expression of transforming growth factor (TGF)-β ligands and receptors and activation of TGF-β signaling, leading to endothelial-to-mesenchymal transition (Endo-MT). We also find that Endo-MT is an important driver of neointima formation in a murine transplant arteriopathy model and in rejection of human transplant lesions. The decline in endothelial FGF signaling input is due to the appearance of an FGF resistance state that is characterized by inflammation-dependent reduction in expression and activation of key components of the FGF signaling cascade. These results establish FGF signaling as a critical factor in maintenance of endothelial homeostasis and point to an unexpected role of Endo-MT in vascular pathology.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2012.10.021
