叉头框转录因子O1在肾纤维化中的作用及其调控

Contribution and Regulation of Forkhead Transcription Factor O1 during the Renal Fibrosis

慢性肾病(chronic kidney disease,CKD)已成为全球不可忽视的一种慢性疾病,而肾的纤维化是CKD的最终结果和关键性病理特征。在CKD的整个过程中均伴随着肾损伤的修复与愈合,且长期慢性刺激会促使肾纤维化逐渐步向肾衰竭,其主要特征是肌成纤维细胞持续活化及细胞外基质过度产生和沉积。肾的纤维化是一个由多种信号分子介导的多种信号通路参与的协同过程,而TGF-β/Smad和Wnt/β-Catenin信号通路是其中最经典的2个。FoxO1是人体中一个重要的转录因子,在多种细胞类型中表达,参与细胞多种生命活动并发挥重要调节作用。目前的研究已经表明,叉头框转录因子O1(forkhead transcription factor O1,FoxO1)在肾纤维化病变中扮演着重要角色。FoxO1可通过STAT、SIRT1、Wnt/β-Catenin、PI-3K/Akt等多种信号通路调控肾纤维化的发生和发展,例如FoxO1/STAT信号可调节TIF和肾小管凋亡;SIRT1/FoxO1信号可调控氧化应激反应和脂肪毒性;FoxO1/β-Catenin可抑制Wnt/β-Catenin信号通路;PI-3K/Akt/FoxO1通路调节炎症反应及糖脂代谢等。另外,一些相关研究表明,FoxO1/Smad很可能在肾的纤维化中发挥了作用。本文综述了FoxO1在肾纤维化中的作用及其分子调控机制,旨在进一步明确肾纤维化的发病机制,从而为CKD的治疗提供新的方向与前景。

Chronic kidney disease(CKD)has become a chronic disease that cannot be ignored all over the world.Renal fibrosis is the final result and key pathological features of CKD.The whole process of renal fibrosis is associated with the repair and healing of kidney damage,and this long-term chronic stimulation promotes the renal fibrosis to the kidney failure,it is characterized by continuous activation of myofibroblasts and excessive production and deposition of extracellular matrix.Renal fibrosis is a synergistic process mediated by a variety of signaling pathways,and TGF-β/Smad and Wnt/β-catenin signaling pathways are two of the most classic ones.FoxO1 is an important transcription factor in the human body,which is expressed in a variety of cell types and plays an important role in a variety of cell life activities.Current researches have shown that FoxO1 plays an important role in renal fibrosis.FoxO1 regulates the occurrence and development of renal fibrosis through various signaling pathways such as STAT,SIRT1,Wnt/β-catenin,PI-3K/Akt.For example,FoxO1/STAT regulates TIF and renal tubule apoptosis,SIRT1/FoxO1 regulates oxidative stress response and lipotoxicity,FoxO1/β-catenin inhibits the Wnt/β-catenin signaling pathway.In addition,some related studies suggest that FoxO1/Smad may play a role in renal fibrosis.The contribution and regulation of FoxO1 in the renal fibrosis are reviewed here in order to further clarify the pathogenesis of renal fibrosis,which may bring new clues and prospects for the treatment of CKD.