Global-feature of autoimmune glomerulonephritis using proteomic analysis of laser capture microdissected glomeruli

Jingjing Dong; Fengping Zheng; Fanna Liu; Jingquan He; Shanshan Li; Wenjun Pu; Huixuan Xu; Zhifeng Luo; Shizhen Liu; Lianghong Yin; Donge Tang; Yong Dai

doi:10.3389/fimmu.2023.1131164

Global-feature of autoimmune glomerulonephritis using proteomic analysis of laser capture microdissected glomeruli

Front Immunol. 2023 Mar 22:14:1131164. doi: 10.3389/fimmu.2023.1131164. eCollection 2023.

Authors

Jingjing Dong^{1

2}, Fengping Zheng^{1

3}, Fanna Liu², Jingquan He¹, Shanshan Li¹, Wenjun Pu¹, Huixuan Xu¹, Zhifeng Luo⁴, Shizhen Liu², Lianghong Yin², Donge Tang¹, Yong Dai^{1

4}

Affiliations

¹ Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong, China.
² Institute of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.
³ Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, China.
⁴ Guangxi Key Laboratory of Metabolic Disease Research, The 924th Hospital of the Chinese People's Liberation Army Joint Logistic Support Force, Guilin, Guangxi, China.

Abstract

Background: IgA nephropathy (IgAN), (LN), membranous nephropathy (MN), and minimal change nephropathy (MCN) are all belonged to autoimmune glomerulonephritis. This study aimed to identify the specific proteomic characteristics of the four GNs diseases in order to provide frameworks for developing the appropriate drug for patients diagnosed with GNs disease.

Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was utilized to investigate proteomic features of glomerular tissues obtained by laser capture microdissection (LCM). 8 normal control cases, 11 IgAN cases, 19 LN cases, 5 MN cases, and 3 MCN cases in this study were selected for bioinformatics analyses.

Results: The shared overlapping proteins among the top 100 DEPs of each GNs type were mostly downregulated, in which only FLII was significantly downregulated in the four GNs diseases. A2M was significantly upregulated in MN, IgAN, and LN subgroups. The pathway of complement and coagulation cascades was notably activated with NES value ranging 2.77 to 3.39 among MCN, MN, IgAN, and LN diseases, but the pattern of protein expression level were significantly different. In LN patients, the increased activity of complement and coagulation cascades was contributed by the high expression of multiple complements (C1QB, C3, C4A, C4B, C6, C8B, C8G, C9). Meanwhile, both C1QC and C4B were remarkably upregulated in MN patients. On the contrary, complement-regulating proteins (CD59) was substantially decreased in MCN and IgAN subgroup.

Conclusions: The integrative proteomics analysis of the four GNs diseases provide insights into unique characteristics of GNs diseases and further serve as frameworks for precision medicine diagnosis and provide novel targets for drug development.

Keywords: IgA nephropathy; autoimmune glomerulonephritis; complement components; laser capture microdissection; lupus nephritis; membranous nephropathy; minimal change nephropathy; proteomic.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chromatography, Liquid
Glomerulonephritis, IGA*
Glomerulonephritis, Membranous*
Humans
Lasers
Nephrosis, Lipoid*
Proteomics / methods
Tandem Mass Spectrometry

Grants and funding

This work was supported by the Guangdong Engineering Technology Research Center (507204531040), Guangzhou Ettex’s academician and expert workstation (0801900000017), Sanming Project of Medicine in Shenzhen (SYJY201704 and SYJY201705), Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties (SZGSP001).