Extracellular matrix directs phenotypic heterogeneity of activated fibroblasts.
Extracellular matrix directs phenotypic heterogeneity of activated fibroblasts.
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DOI：
10.1016/j.matbio.2017.12.003
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发表时间：
2018-04
期刊：
影响因子：
--
通讯作者：
Puré E
中科院分区：
文献类型：
--
作者：
Avery D;Govindaraju P;Jacob M;Todd L;Monslow J;Puré E
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.
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影响因子：
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作者：
Beacham, Dorothy A;Amatangelo, Michael D;Cukierman, Edna
通讯作者：
Cukierman, Edna
影响因子：
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作者：
Cukierman, E;Pankov, R;Yamada, KM
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通讯作者：
Larrinaga G
DOI：
10.3791/2089
发表时间：
2010-08-10
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
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通讯作者：
Assoian, Richard