足细胞足突融合消失和蛋白尿是肾小球疾病的共同特征,了解足细胞的生物学特性,对研究足细胞损伤机制、靶向治疗具有重要意义.裂孔隔膜作为足细胞重要组成部分之一,对维持肾小球滤过屏障结构及功能、限制蛋白滤过起关键作用.CD2相关蛋白(CD2AP)作为裂孔隔膜的代表性蛋白之一,与细胞骨架相关蛋白、其他裂孔隔膜蛋白、基底膜区蛋白、顶膜区蛋白和离子通道蛋白存在相互作用,共同影响足细胞形态学和动力学.本文围绕CD2 AP与足细胞相关蛋白的相互作用进行综述,为探讨蛋白尿的发生机制提供参考.

Objective:To analyze the mutation sites and characteristics of phospholipase CE1( PLCE1) gene in children with primary nephrotic syndrome(PNS) in Zhuang, Guangxi, China, so as to explore the expression status of PLCE1 protein in peripheral blood of PNS patients. Methods:(1)Blood samples of 154 Zhuang children with PNS and 98 healthy children of Zhuang nationality from July 2015 to September 2017 in Affiliated Hospital of Youjiang Medical College for Nationalities were collected to sequence PLCE1 gene with FastTarget target gene capture method in the combination with next generation sequencing.Based on the comparison between mutation results and information from the database, the pathogenicity, phenotype and distribution characteristics of these mutation sites were discovered and appraised.(2)The concentration of PLCE1 protein in serum samples were measured by enzyme-linked immuno sorbent assay, then the data of PNS group and healthy control group were compared and analyzed statistically with SPSS 25.0. Results:(1)A total of 18 low-frequency mutations of PLCE1 were observed, 5 of them(c.670C>T, c.578T>C, c.923G>T, c.4916C>T, and c. 5927_5929del) were found only in the PNS group, and 3 of them occurred in both PNS group and healthy control group: c.176C>T, c.389T>C, and c. 4304C>T.Five newly discovered mutations (c.923G>T, c.958T>A, c.1151C>T, c.2341A>G, and c. 3592G>C)were discovered and only c. 923 G>T is pathogenic mutation of PLCE1.(2)The concentration of PLCE1 protein in healthy control group was 414.65 (231.20, 729.81) ng/L and the level of PLCE1 in PNS group was 237.84 (116.14, 535.85) ng/L, ( Z=-3.212, P<0.001), and the value of PNS group was lower than that in the healthy control group. Conclusions:(1)As a new pathogenic mutation of PLCE1, c.923G>T was found.(2)The phenotype of PLCE1 gene mutation in Zhuang children with PNS was diverse, and they may differ by race and region.(3) PLCE1 protein of serum may act as a protective protein to guarantee various life activities of cells by participating in multiple signal transduction pathways.

多种因素可以导致足细胞损伤,如感染、毒物或药物、代谢紊乱、血流动力学改变、基因突变引起足细胞相关蛋白改变、免疫相关性损伤等.在这些损伤因素作用下,足细胞可发生足突融合、去分化、脱落凋亡、发育停滞等.随着对足细胞结构和功能的深入了解,其在肾小球疾病中的作用机制越来越清晰,足细胞损伤靶向干预成为研究的新方向之一.CD2相关蛋白(CD2-associated protein,CD2AP)作为构成肾小球足细胞裂孔隔膜的成分之一,在保持肾小球滤过屏障完整性方面发挥重要作用,其表达水平或结构改变可引起足细胞一系列病理生理改变,从而出现大量蛋白尿,甚至导致肾功能衰竭进而死亡.综述了靶向干预CD2 AP对足细胞损伤的影响.