TGF-β signaling in fibrosis.

TGF-β signaling in fibrosis.
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DOI:
10.3109/08977194.2011.595714
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发表时间:
2011-10
期刊:
Growth factors (Chur, Switzerland)
影响因子:
--
通讯作者:
Frangogiannis NG
Frangogiannis NG
中科院分区:
其他
文献类型:
--
作者:
Biernacka A;Dobaczewski M;Frangogiannis NG

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转化生长因子β(Transforming growth factor β,TGF-β)是纤维化发生的重要介质。TGF-β在纤维化疾病中被上调和激活,并调节成纤维细胞表型和功能,诱导肌成纤维细胞转分化,同时促进基质保存。在广泛的实验模型中的研究已经证明了典型的ALK 5/Smad 3通路参与纤维化。Smad非依赖性通路可以调节Smad的激活,并且在某些条件下,可以直接抑制纤维化信号。TGF-β的促纤维化作用至少部分地通过诱导其下游效应物结缔组织生长因子来介导。鉴于其在纤维化发病机制中的重要作用,TGF-β已成为有吸引力的治疗靶点。然而,TGF-β的多效性和多功能作用及其在组织稳态、免疫和细胞增殖中的作用引起了对可能由TGF-β阻断引起的潜在副作用的关注。本文综述了TGF-β信号通路在纤维化反应中的作用。
Transforming growth factor β (TGF-β) is a central mediator of fibrogenesis. TGF-β is upregulated and activated in fibrotic diseases and modulates fibroblast phenotype and function, inducing myofibroblast transdifferentiation while promoting matrix preservation. Studies in a wide range of experimental models have demonstrated the involvement of the canonical ALK5/Smad3 pathway in fibrosis. Smad-independent pathways may regulate Smad activation and, under certain conditions, may directly transduce fibrogenic signals. The profibrotic actions of TGF-β are mediated, at least in part, through induction of its downstream effector, Connective Tissue Growth Factor. In light of its essential role in the pathogenesis of fibrosis, TGF-β has emerged as an attractive therapeutic target. However, the pleiotropic and multifunctional effects of TGF-β and its role in tissue homeostasis, immunity and cell proliferation raise concerns regarding potential side effects that may be caused by TGF-β blockade. This minireview summarizes the role of TGF-β signaling pathways in the fibrotic response.
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