Evidence map›Paper›PMID 40146438›Full record

ArticleMolecular biology reports2025

Identification of c-Jun phosphorylation as a crucial mediator of complement activation in renal ischemia-reperfusion injury revealed by phosphoproteomics and functional validation.

Yufeng Zhao, Yirui Cao, Ying Su, Juntao Chen, Xuanchuan Wang, Peipei Ding, Weiguo Hu, Tongyu Zhu, Chao Hu

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Article in Molecular biology reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

9 authors.

Yufeng Zhao *Department of Kidney Transplantation, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
Yirui Cao *Department of Kidney Transplantation, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
Ying Su *Cardiac Intensive Care Center, Zhongshan Hospital, Fudan University, Shanghai, China.
Juntao ChenDepartment of Kidney Transplantation, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
Xuanchuan WangDepartment of Kidney Transplantation, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
Peipei DingFudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Fudan University, Shanghai, China.
Weiguo HuFudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Fudan University, Shanghai, China. weiguohu@fudan.edu.cn.
Tongyu ZhuDepartment of Kidney Transplantation, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. zhu.tongyu@zs-hospital.sh.cn.
Chao HuDepartment of Kidney Transplantation, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. chaohu1988@hotmail.com.

Funding

Clinical Research Funds of Zhongshan Hospital ZSLCYJ202335Natural Science Foundation of China 81900682Natural Science Foundation of Shanghai Municipality 21ZR1412900Shanghai Key Laboratory of Organ Transplantation 2023XKPT04Shanghai Municipal Key Clinical Specialty shslczdzk05802Shanghai Sailing Program 19YF1406600
6 · The paper itself

Abstract

backgroundIschemia reperfusion injury (IRI) is an unavoidable condition that primarily affects graft function in renal transplantation. Blockage of complement activation by complement receptor immunoglobulin/ factor H (CRIg/FH), a novel complement inhibitor, shows great potency to ameliorate renal IRI. Sublytic membrane attack complex (MAC) disrupts cellular functions via the activation of different protein kinases and phosphorylation of critical signal transduction factors. We aimed to investigate whether complement activation triggered shift in phosphorylation status in IRI. METHODS AND

resultsWe performed a LC-MS/MS-based quantitative phosphoproteomic analysis of CRIg/FH-IRI, PBS-IRI and Sham mice, depicting a thorough protein phosphorylation profile. C3d and MAC staining were conducted to study the complement activation status. In vitro model mimicking complement mediated IRI tubular injury was achieved by applying normal human serum (NHS) to TCMK cells. By hierarchical clustering, we observed that CRIg/FH treatment reversed the hyperphosphorylation status triggered by IRI. Differentially expressed phosphoproteins (DEPs) were associated with focal adhesion, integrin activation, actin cytoskeleton organization and cell junction. We identified c-Jun as the most differentially phosphorylated transcriptional factor regulated by complement activation, the S63 phosphorylation of which was verified both in vitro and in vivo and screened for its downstream targets. JNK inhibitor reduced the phosphorylation of c-Jun and attenuated accumulation of the C3d on the tubular epithelial cells.

conclusionWe proposed a crucial role of c-Jun phosphorylation in complement activation induced by renal IRI by combining phosphoproteomic approaches and protein validation, which hopefully could provide novel insights into the pathological mechanisms of IRI.

Indexed as

Complement ActivationProto-Oncogene Proteins c-junReperfusion InjuryAnimalsDisease Models, AnimalHumansKidneyMaleMiceMice, Inbred C57BLPhosphoproteinsPhosphorylationProteomicsSignal TransductionTandem Mass SpectrometryPhosphoproteinsProto-Oncogene Proteins c-junc-JunComplementIschemia reperfusion injuryMembrane attack complexPhosphorylation

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.