Fstl1-TGF-β1-Smad2/3信号通路与肺纤维化的靶向治疗

Fstl1-TGF-β1-Smad2/3 signaling pathway and the target therapy for pulmonary fibrosis

肺纤维化是以上皮细胞受损、成纤维细胞增殖活化、细胞外基质聚积、肺泡不可逆破坏为特点的肺间质性疾病,其发病机制尚不十分确切,常规药物治疗疗效不显著。研究发现,转化生长因子β(TGF-β1)在肺纤维化发生发展中起到关键作用,而TGF-β1-Smad2/3通路是TGF-β1信号传导的经典通路,Fstl1-TGF-β1-Smad2/3信号通路与肺纤维化密切相关,通过某一靶点阻断其信号通路可以抑制肺纤维化的进程;而Fstl1可以通过调节TGF-β1/Smad2/3信号通路来调控成纤维细胞活化和细胞外基质合成,具有促纤维化作用。通过某一靶点阻断其信号通路可以抑制肺纤维化的进程。Fstl1-TGF-β1-Smad2/3信号的传导与调控是一个涉及多靶点的复杂过程。笔者对肺纤维化中TGF-β信号传导通路及其靶向治疗做一综述,为抗肺纤维化治疗提供参考。

Pulmonary fibrosis are interstitial lung diseases prodominated by damage of epithelial cells,proliferation and activation of fibroblasts,accumulation of extracellular matrix and irreversible destruction of alveolus.Their etiology and pathogenesis are not very exact yet.The curative effect of conventional medication is not significant.Recent studies have found that TGF beta plays a crucial role in the development of pulmonary fibrosis;TGF-beta 1-Smad2/3 pathway is the classic pathway of TGF-beta 1 signal transduction,meanwhile Fstl1-TGF-beta 1-Smad2/3 signaling pathway is closely related to pulmonary fibrosis.Blocking its signal pathway through a target can inhibit pulmonary fibrosis.Fstl1 can regulate fibroblast activation and extracellular matrix synthesis by regulating TGF-beta 1/Smad2/3 signaling pathway,which having the effect of promoting fibrosis.Blocking the signaling pathway through a target can inhibit the progression of pulmonary fibrosis.The transmission and regulation of Fstl1-TGF-beta 1-Smad2/3 signal is a complex process involving multiple targets.So,authors reviewe the target therapy of pulmonary fibrosis and its TGF-βsignaling pathway,so that provlding reference for treating this disease.