转化生长因子-β信号通路在疾病发生发展中作用的研究状况

Study on the role of transforming growth factor-β/Smads signaling pathway in the occurrence and development of diseases

纤维化疾病、肿瘤及糖尿病肾病等多种疾病在世界范围内困扰着患者,严重影响了患者的生活质量,造成了极大的经济负担。转化生长因子-β(TGF-β)/Smads信号通路在这些疾病中起着关键性的作用,TGF-β控制许多细胞功能,包括增殖、凋亡、分化、上皮-间充质转化(EMT)和迁移,在胚胎发生和成体组织稳态中发挥关键作用。在纤维化疾病中,TGF-β/Smads信号通路的激活使得成纤维细胞增殖分化为肌成纤维细胞,合成大量胶原蛋白,致使细胞外基质(ECM)过度沉积,导致纤维化疾病的发生。在肿瘤的发生发展中,TGF-β/Smads信号通路激活后,TGF-β1高表达,诱导EMT,导致癌相关成纤维细胞(CAFs)形成,加速了肿瘤微环境(TME)的构建,促进了肿瘤的侵袭。在糖尿病肾病中,糖尿病环境增强氧化应激,诱导TGF-β1的表达,激活TGF-β/Smads信号通路,促进系膜细胞肥大和ECM积聚,降低肾小球滤过率,导致肾间质纤维化和肾小球硬化,最终发展为慢性肾功能衰竭。本文就近年来TGF-β/Smads信号通路在多种疾病中的作用机制进行了综述。

Fibrotic disease,tumor,diabetic nephropathy and other diseases are plaguing patients all over the world,seriously affecting the quality of life of patients,resulting in a great economic burden.Transforming growth factor-β(TGF-β)/Smads signaling pathway plays a key role in these diseases.TGF-β controls many cellular functions,including proliferation,apoptosis,differentiation,epithelial-mesenchymal transformation(EMT)and migration,and plays a key role in embryogenesis and adult tissue homeostasis.In fibrotic diseases,the activation of TGF-β/Smads signaling pathway leads to the proliferation and differentiation of fibroblasts into myofibroblasts and the synthesis of large amounts of collagen,resulting in excessive deposition of extracellular matrix(ECM)and the occurrence of fibrotic diseases.In the occurrence and development of tumors,TGF-β1 is highly expressed after the activation of TGF-β/Smads signaling pathway,inducing EMT,leading to the formation of cancer-associated fibroblasts(CAFs),accelerating the construction of tumor microenvironment(TME),and promoting tumor invasion.In diabetic nephropathy,the diabetic environment enhances oxidative stress,induces TGF-β1 expression,activates TGF-β/Smads signaling pathway,promotes mesangial cell hypertrophy and ECM accumulation,reduces glomerular filtration rate,leads to renal interstitial fibrosis and glomerular sclerosis,and eventually develops into chronic renal failure.In this paper,the role of TGF-β/Smads signaling pathway in a variety of diseases was reviewed in recent years.