细胞G2/M周期阻滞与肾间质纤维化

G2/M cell cycle arrest and renal interstitial fibrosis

慢性肾脏病(CKD)是威胁人类公共健康的重大疾病之一,肾间质纤维化是各种CKD进展至终末期肾病的共同病理表现。然而肾间质纤维化的病理机制还有待阐明,临床也缺乏针对肾间质纤维化有效的治疗方法。越来越多研究表明,肾小管上皮细胞G2/M周期阻滞是肾间质纤维化发生发展中的一个重要事件。在多种肾损伤模型中,均发现肾小管上皮细胞G2/M周期阻滞和肾脏纤维化的因果关系,逆转细胞G2/M周期阻滞成为缓解肾脏纤维化的潜在靶点。此外,相关机制研究表明,包括丝裂原活化蛋白激酶(MAPK)、自噬等在内的诸多信号通路与细胞G2/M周期阻滞密切关联,共同影响肾间质纤维化的发生与进展。本文就细胞G2/M周期阻滞参与肾间质纤维化的最新研究作一综述,以期为CKD的临床诊治和新药研发提供思路。

Chronic kidney disease is one of the major diseases threatening public health. Renal interstitial fibrosis(RIF) is a common pathological manifestation of various chronic kidney diseases in the end stage. However, the pathological mechanism of RIF remains to be clarified, and there is a lack of effective treatment for that. Increasing studies have shown that G2/M cycle arrest of renal tubular epithelial cells is an important event in the occurrence and development of RIF. In a variety of renal injury models, the causal relationship between G2/M cycle arrest of renal tubular epithelial cells and renal fibrosis has been found. Reversing G2/M cycle arrest has become a potential target to alleviate renal fibrosis. In addition, studies suggested that various pathways, including MAPK and autophagy, are closely related to G2/M cycle arrest, they affect the occurrence and progress of RIF collectively. This paper reviews the latest research on the involvement of G2/M cycle arrest in RIF, in order to provide ideas for the clinical diagnosis and treatment of chronic kidney disease and the development of new drugs.