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

Autor: Zhang F; Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China., Li P; Department of Pathology, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China., Shan Y; Clinical Research Academy, Peking University Shenzhen Hospital, Peking University, Shenzhen, Guangdong Province, China., Lai Z; Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China., Hou S; Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China., Xiong Z; Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China., Xiong Z; Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China., Huang X; Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China. huangxiaoyan@pku.org.cn., Zheng F; Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China. pennycheng01@163.com.; Department of Rheumatology and Immunology, Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen People's Hospital (The Second Clinical Medical College of Jinan University, The First Affiliated Hospital Southern University of Science and Technology), Shenzhen, China. pennycheng01@163.com.
Jazyk: angličtina
Zdroj: Clinical rheumatology [Clin Rheumatol] 2024 Nov; Vol. 43 (11), pp. 3551-3564. Date of Electronic Publication: 2024 Sep 16.
DOI: 10.1007/s10067-024-07140-x
Abstrakt: Introduction: The 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.
Method: In this study, we employed label-free quantitative proteomics based on mass spectrometry to generate kidney protein profiles with varying CI scores.
Results: A 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-κB, JNK, PI3K/AKT/mTOR signaling pathway, lipoprotein biosynthetic process, and endocytosis, in both subgroups.
Conclusion: In 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 • Fibrosis is a fundamental and characteristic pathological process underlying the NIH-CI in LN. • Different EMT status presented variant clinical characteristics, immune features in LN.
(© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)
Databáze: MEDLINE
Externí odkaz: