Targeted Metabolomics Study of Human Plasma Revealed Activation of the Cytochrome P450 Epoxygenase/Epoxide Hydrolase Axis in Patients with IgA Nephropathy

作者全名："Deng, Bing-Qing; Li, Meng-Yuan; Fu, Xian; Luo, Ying; Qiao, Qing; Liu, Jun-Yan"

作者地址："[Deng, Bing-Qing; Qiao, Qing] Soochow Univ, Div Nephrol, Dushu Lake Hosp, Suzhou 215135, Peoples R China; [Li, Meng-Yuan] Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Nephrol, Sch Med, Hangzhou 310016, Peoples R China; [Fu, Xian; Liu, Jun-Yan] Chongqing Med Univ, Inst Life Sci, Ctr Novel Target & Therapeut Invent, Chongqing 400016, Peoples R China; [Luo, Ying] East China Normal Univ, Changning Matern & Infant Hlth Hosp, Dept Clin Lab, Shanghai 200050, Peoples R China"

通信作者："Qiao, Q (通讯作者)，Soochow Univ, Div Nephrol, Dushu Lake Hosp, Suzhou 215135, Peoples R China.; Liu, JY (通讯作者)，Chongqing Med Univ, Inst Life Sci, Ctr Novel Target & Therapeut Invent, Chongqing 400016, Peoples R China."

来源：JOURNAL OF PROTEOME RESEARCH

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000879545300001

JCR分区：Q1

影响因子：4.4

年份：2022

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：CYP epoxygenase; epoxide hydrolase; IgA nephropathy; metabolomics; oxylipin profile

摘要："IgA nephropathy (IgAN) is the most common primary glomerulonephritis and a leading cause of chronic kidney disease. The pathogenic mechanism of IgAN remains largely unknown and thus a specific therapeutic target is lacking. Here, we reported that the cytochrome P450 (CYP) epoxygenase/epoxide hydrolase (EH) axis was activated in the patients and is likely a therapeutic target for IgAN. Specifically, quantitative profiling of the plasma from IgAN patients and healthy controls revealed significant changes in plasma levels of CYP/EH-mediated lipid epoxides and diols. Subsequently, CYP2C8, CYP2C18, CYP2J2, EPHX1, and EPHX2 were found to be significantly increased in whole blood cells at mRNA levels from the IgAN patients when compared with those of healthy controls. Immunohistochemical analysis showed that all five CYPs and two EHs were upregulated in the kidney tissue from IgAN patients when compared with normative renal tissue, but the expression locations of the proteins were different with most of them. Treatment of HK-2 cells with IgA1 increased cell viability, compressed cell apoptosis, and increased the protein levels of CYP2C9, EPHX1, and EPHX2. All the results agreed that CYPs/EHs axis is likely the prophylactic and therapeutic target for IgAN, providing IgAN patients with a new intervention strategy."

基金机构：Shanghai National Sciences Foundation [19ZR1439800]; Chongqing Human Resources and Social Security Bureau Entrepreneurship and Innovation Support Program [2204012978989154]; Chongqing Medical University

基金资助正文："This project was co-supported by Shanghai National Sciences Foundation (19ZR1439800) , Chongqing Human Resources and Social Security Bureau Entrepreneurship and Innovation Support Program for Oversea Returnees (2204012978989154) , and a Startup grant for high-level talents from Chongqing Medical University. We would like to thank all the patients and healthy volunteers for participating in this study, as well as the doctors, nurses, and technical staff for diagnosis and blood collection."