G2/M细胞周期阻滞在急性肾损伤向慢性肾脏病转变中的作用研究进展

Research progress on the role of G2/M cell cycle arrest in the AKI-CKD transition

急性肾损伤(acute kidney injury,AKI)的发病率和病死率都很高。研究发现,AKI是慢性肾脏病(chronic kidney disease,CKD)发生的独立危险因素。氧化应激、内质网应激、巨噬细胞极化及肾小管细胞周期阻滞均参与了AKI向CKD进展的病理生理过程。越来越多的证据表明,肾小管上皮细胞周期阻滞可能在纤维化的发展中发挥重要作用。事实上,在肾损伤后的适应不良修复过程中,许多正在进行细胞分裂的肾小管细胞在细胞周期的G2/M期会延长一段时间。本文综述了ARI后的不适应修复,其主要机制是G2/M期阻滞及参与G2/M期阻滞调控的相关因子,导致进行性肾脏纤维化的发展。

Acute kidney injury(AKI)is an increasingly common complication during hospitalization with high morbidity and mortality.In recent years,it has been found that AKI is an independent risk factor for chronic kidney disease(CKD).Studies show that oxidative stress,endoplasmic reticulum stress,macrophage polarization and tubule cell cycle arrest are all involved in the pathophysiological process of progression from AKI to CKD.Increasing evidence suggests that renal tubular epithelial cell cycle arrest may play an important role in the progression of fibrosis.Indeed,during the maladaptive repair after a renal injury,many tubular cells that are undergoing cell division spend a prolonged period in the G2/M phase of the cell cycle.This article reviews the maladaptive repair after AKI,which is mainly caused by G2/M cell cycle arrest and the related factors involved in the regulation of G2/M arrest,leading to the development of progressive renal fibrosis.