The important roles and molecular mechanisms of annexin A(2) autoantibody in children with nephrotic syndrome

doi:10.21037/atm-21-3988

科研成果详情

题名	The important roles and molecular mechanisms of annexin A(2) autoantibody in children with nephrotic syndrome
作者	Ye, Qing 1; Zhang, Yingying 2; Zhuang, Jieqiu3,4; Bi, Ye 3,4; Xu, Hong 5; Shen, Qian 5; Liu, Jialu 5; Fu, Haidong 2; Wang, Jingjing 2; Feng, Chunyue 2; Tang, Xiaoxiao 2; Liu, Fei 2; Gu, Weizhong 6; Zhao, Fei 7; Zhang, Jianjiang 8; Qin, Yuanhan 9; Shang, Shiqiang 1; Shen, Hongqiang 1; Chen, Xuejun 1; Shen, Huijun 2; Liu, Aimin 2; Xia, Yonghui 2; Lu, Zhihong 2; Shu, Qiang 10; Mao, Jianhua 2
发表日期	2021-09
发表期刊	ANNALS OF TRANSLATIONAL MEDICINE 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Chronic kidney disease nephrotic syndrome pediatric nephrology podocyte cytoskeleton
其他关键词	CELL ; PODOCYTE ; PHOSPHORYLATION ; PATHOGENESIS ; A2
摘要	Background: In recent years, B-cell dysfunction has been found to play an important role in the pathogenesis of primary nephrotic syndrome (PNS). B cells play a pathogenic role by secreting antibodies against their target antigens after transforming into plasma cells. Therefore, this study aimed to screen the autoantibodies that cause PNS and explore their pathogenic mechanisms. Methods: Western blotting and mass spectrometry were employed to screen and identify autoantibodies against podocytes in children with PNS. Both in vivo and in vitro experiments were used to study the pathogenic mechanism of PNS. The results were confirmed in a large multicenter clinical study in children. Results: Annexin A(2) autoantibody was highly expressed in children with PNS with a pathological type of minimal change disease (MCD) or focal segmental glomerulosclerosis without genetic factors. The mouse model showed that anti-Annexin A(2) antibody could induce proteinuria in vivo. Mechanistically, the effect of Annexin A(2) antibody on the Rho signaling pathway was realized through promoting the phosphorylation of Annexin A(2) at Tyr24 on podocytes by reducing its binding to PTP1B, which led to the cytoskeletal rearrangement and damage of podocytes, eventually causing proteinuria and PNS. Conclusions: Annexin A(2) autoantibody may be responsible for some cases of PNS with MCD/FSGS in children.
资助项目	Key Project of Provincial Ministry Co-Construction, Health Science and Technology Project Plan of Zhejiang Province [WKJ-ZJ-2128]; Key Laboratory of Women's Reproductive Health Research of Zhejiang Province [ZDFY2020-RH-0006]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81501760, 81470939, 81270792, 81170664]; Key Research and Development Plan of Zhejiang Province [2019C03028]
出版者	AME PUBL CO
出版地	SHATIN
ISSN	2305-5839
EISSN	2305-5847
卷号	9 期号:18 页码:1452
DOI	10.21037/atm-21-3988
页数	22
WOS类目	Oncology ; Medicine, Research & Experimental
WOS研究方向	Oncology ; Research & Experimental Medicine
WOS记录号	WOS:000696978900001
收录类别	SCIE ; PUBMED
URL	查看原文
PubMed ID	34734004
PMC记录号	PMC8506724
通讯作者地址	[Mao, Jianhua]Zhejiang Univ, Natl Clin Res Ctr Child Hlth, Dept Nephrol, Childrens Hosp,Sch Med, Hangzhou 310052, Peoples R China. ; [Shu, Qiang]Zhejiang Univ, Natl Clin Res Ctr Child Hlth, Dept Thorac & Cardiovasc Surg, Childrens Hosp,Sch Med, Hangzhou 310052, Peoples R China.
引用统计	被引频次：6[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/19950
专题	附属第二医院_儿童肾脏科第二临床医学院，附属第二医院、育英儿童医院
通讯作者	Shu, Qiang; Mao, Jianhua
作者单位	1.Zhejiang Univ, Natl Clin Res Ctr Child Hlth, Dept Clin Lab, Childrens Hosp,Sch Med, Hangzhou, Peoples R China; 2.Zhejiang Univ, Natl Clin Res Ctr Child Hlth, Dept Nephrol, Childrens Hosp,Sch Med, Hangzhou 310052, Peoples R China; 3.Wenzhou Med Univ, Dept Pediat Nephrol, Affiliated Hosp 2, Wenzhou, Peoples R China; 4.Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou, Peoples R China; 5.Fudan Univ, Natl Pediat Med Ctr China, Childrens Hosp, Dept Nephrol, Shanghai, Peoples R China; 6.Zhejiang Univ, Natl Clin Res Ctr Child Hlth, Dept Pathol, Childrens Hosp,Sch Med, Hangzhou, Peoples R China; 7.Nanjing Med Univ, Childrens Hosp, Dept Nephrol, Nanjing, Peoples R China; 8.Zhengzhou Univ, Affiliated Hosp 1, Dept Pediat, Zhengzhou, Peoples R China; 9.Guangxi Med Univ, Dept Pediat Nephrol, Affiliated Hosp 1, Nanning, Peoples R China; 10.Zhejiang Univ, Natl Clin Res Ctr Child Hlth, Dept Thorac & Cardiovasc Surg, Childrens Hosp,Sch Med, Hangzhou 310052, Peoples R China
推荐引用方式 GB/T 7714	Ye, Qing,Zhang, Yingying,Zhuang, Jieqiu,et al. The important roles and molecular mechanisms of annexin A(2) autoantibody in children with nephrotic syndrome[J]. ANNALS OF TRANSLATIONAL MEDICINE,2021,9(18):1452.
APA	Ye, Qing., Zhang, Yingying., Zhuang, Jieqiu., Bi, Ye., Xu, Hong., ... & Mao, Jianhua. (2021). The important roles and molecular mechanisms of annexin A(2) autoantibody in children with nephrotic syndrome. ANNALS OF TRANSLATIONAL MEDICINE, 9(18), 1452.
MLA	Ye, Qing,et al."The important roles and molecular mechanisms of annexin A(2) autoantibody in children with nephrotic syndrome".ANNALS OF TRANSLATIONAL MEDICINE 9.18(2021):1452.