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- W2774304513 abstract "Activated fibroblasts are key players in the injury response, tumorigenesis, fibrosis, and inflammation. Dichotomous outcomes in response to varied stroma-targeted therapies in cancer emphasize the need to disentangle the roles of heterogeneous fibroblast subsets in physiological and pathophysiological settings. In wound healing, fibrosis, and myriad tumor types, fibroblast activation protein (FAP) and alpha-smooth muscle actin (αSMA) identify distinct, yet overlapping, activated fibroblast subsets. Prior studies established that FAPHi reactive fibroblasts and αSMAHi myofibroblasts can exert opposing influences in tumorigenesis. However, the factors that drive this phenotypic heterogeneity and the unique functional roles of these subsets have not been defined. We demonstrate that a convergence of ECM composition, elasticity, and transforming growth factor beta (TGF-β) signaling governs activated fibroblast phenotypic heterogeneity. Furthermore, FAPHi reactive fibroblasts and αSMAHi myofibroblasts exhibited distinct gene expression signatures and functionality in vitro, illuminating potentially unique roles of activated fibroblast subsets in tissue remodeling. These insights into activated fibroblast heterogeneity will inform the rational design of stroma-targeted therapies for cancer and fibrosis." @default.
- W2774304513 created "2017-12-22" @default.
- W2774304513 creator A5004098027 @default.
- W2774304513 creator A5016493527 @default.
- W2774304513 creator A5033766002 @default.
- W2774304513 creator A5053572696 @default.
- W2774304513 creator A5077546736 @default.
- W2774304513 creator A5078317783 @default.
- W2774304513 date "2018-04-01" @default.
- W2774304513 modified "2023-10-16" @default.
- W2774304513 title "Extracellular matrix directs phenotypic heterogeneity of activated fibroblasts" @default.
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