Unraveling the proteomic landscape of fibrosis in lupus nephritis through CI-based analysis

Zhang, Fan1; Li, Ping2; Shan, Ying3; Lai, Zhiwei1; Hou, Shuang1; Xiong, Zibo1; Xiong, Zuying1; Huang, Xiaoyan1; Zheng, Fengping1,4

2024-09-01

10.1007/s10067-024-07140-x

CLINICAL RHEUMATOLOGY   影响因子和分区

0770-3198

1434-9949

IntroductionThe underlying mechanism by which lupus nephritis (LN) progresses to chronic kidney disease remains elusive. Fibrosis is a hallmark feature of chronic kidney disease, including LN. The chronicity index (CI) score, which incorporates glomerular sclerosis, fibrous crescents, tubular atrophy, and interstitial fibrosis, summarizes the extent of kidney tissue fibrosis.MethodIn this study, we employed label-free quantitative proteomics based on mass spectrometry to generate kidney protein profiles with varying CI scores.ResultsA total of 98 proteins exhibiting linear correlation with CI scores were initially screened out by linear model (CI linearly related proteins), and subsequently, 12 key proteins were derived based on the CI linearly related proteins using Cytohubba. LN patients were stratified into two subtypes based on CI scores and epithelial-mesenchymal transition (EMT) characteristics. These subtypes exhibited significant disparities in immune infiltration and molecular pathways. The high EMT group exhibited heightened activation of immune cells, such as memory B cells, gamma delta T cells, and resting mast cells. Gene Set Enrichment Analysis (GSEA) uncovered substantial dysregulation in critical biological processes and signaling pathways, including NF-kappa B, JNK, PI3K/AKT/mTOR signaling pathway, lipoprotein biosynthetic process, and endocytosis, in both subgroups.ConclusionIn conclusion, this study establishes molecular subgroups based on the CI score, providing novel insights into the molecular mechanisms governing chronicity in the kidneys of diverse LN patients.Key Points center dot Fibrosis is a fundamental and characteristic pathological process underlying the NIH-CI in LN.center dot Different EMT status presented variant clinical characteristics, immune features in LN.ConclusionIn conclusion, this study establishes molecular subgroups based on the CI score, providing novel insights into the molecular mechanisms governing chronicity in the kidneys of diverse LN patients.Key Points center dot Fibrosis is a fundamental and characteristic pathological process underlying the NIH-CI in LN.center dot Different EMT status presented variant clinical characteristics, immune features in LN.

Chronicity index Epithelial-mesenchymal transition Immune cells Lupus nephritis

SCI

英语

通讯

Shenzhen Science and Technology Innovation Commission[JCYJ20200109140412476] ; National Natural Science Foundation of China[82302042] ; Sanming Project of Medicine in Shenzhen[SZSM201812097]

Rheumatology

Rheumatology

WOS:001314126900002

SPRINGER LONDON LTD

Web of Science

1.Peking Univ, Shenzhen Hosp, Dept Nephrol, Shenzhen, Guangdong, Peoples R China
2.Peking Univ, Shenzhen Hosp, Dept Pathol, Shenzhen, Guangdong, Peoples R China
3.Peking Univ, Shenzhen Hosp, Clin Res Acad, Shenzhen, Guangdong, Peoples R China
4.Southern Univ Sci & Technol, Clin Med Coll 2, Shenzhen Peoples Hosp, Dept Rheumatol & Immunol,Dept Clin Med Res Ctr,Gua, Shenzhen, Peoples R China

Zhang, Fan,Li, Ping,Shan, Ying,et al. Unraveling the proteomic landscape of fibrosis in lupus nephritis through CI-based analysis[J]. CLINICAL RHEUMATOLOGY,2024.

Zhang, Fan.,Li, Ping.,Shan, Ying.,Lai, Zhiwei.,Hou, Shuang.,...&Zheng, Fengping.(2024).Unraveling the proteomic landscape of fibrosis in lupus nephritis through CI-based analysis.CLINICAL RHEUMATOLOGY.

Zhang, Fan,et al."Unraveling the proteomic landscape of fibrosis in lupus nephritis through CI-based analysis".CLINICAL RHEUMATOLOGY (2024).