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 activin receptor-like kinase 5/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.

中文翻译：

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纤维化中的 TGF-β 信号转导。

转化生长因子 β (TGF-β) 是纤维发生的中心介质。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表明，经典激活素受体样激酶 5/Smad3 通路参与纤维化。不依赖 Smad 的通路可以调节 Smad 激活，并且在某些条件下可以直接转导纤维生成信号。TGF-β 的促纤维化作用至少部分是通过诱导其下游效应物结缔组织生长因子来介导的。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人们对 TGF-β 阻断可能引起的潜在副作用的担忧。这篇小综述总结了 TGF-β 信号通路在纤维化反应中的作用。