Evidence map›Paper›PMID 42694969›Full record

ArticleInternational journal of biological sciences2026

Enhanced WWP2 Exacerbates Podocyte Injury in Lupus Nephritis through Monoubiquitylating H2A at K119.

Ran You, Yuteng Jiang, Yingyi Xu, Qianying Liu, Menglei Gu, Yue Zhang, Zhanjun Jia, Mengqiu Wu, Mi Bai, Aihua Zhang

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In one paragraph

Article in International journal of biological sciences, 2026. 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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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Ran YouNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
Yuteng JiangNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
Yingyi XuNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
Qianying LiuNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
Menglei GuNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
Yue ZhangNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
Zhanjun JiaNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
Mengqiu WuNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
Mi BaiNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.
Aihua ZhangNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Podocyte injury drives proteinuria in lupus nephritis (LN). Targeting therapy against podocyte injury in LN is in demand. The E3 ubiquitin ligase WWP2 has context-dependent roles in renal tubulointerstitial injury and repair; however, since immune disorder-induced podocyte injury has distinct pathological foundations than tubulointerstitial pathology, WWP2's function in podocytes and LN remains unknown. Here we found that WWP2 protein levels significantly increased in the glomeruli of LN kidneys and were correlated with proteinuria in patients. Renal WWP2 knockdown alleviated, while its overexpression exacerbated proteinuria and podocyte injury in MRL/lpr mice. Podocyte-specific WWP2 deficiency protected against proteinuria in the NTS model. Mechanistically, multi-omics analysis revealed WWP2's association with systemic lupus erythematosus pathways and histone H2A. We identified WWP2 as a novel E3 ligase that monoubiquitylated H2A at K119 (ub-H2A). Ub-H2A levels increased in LN glomeruli, depended on WWP2, and mediated WWP2-aggravated podocyte injury. This effect involved alteration of actin dynamics via FAK signaling. Finally, a novel WWP2 inhibitor attenuated proteinuria in nephritic mice. In conclusion, the WWP2/ub-H2A axis promotes podocyte injury in LN by disrupting actin dynamics. Targeting this pathway represents a potential therapeutic strategy for LN.

Indexed as

HistonesLupus NephritisPodocytesUbiquitin-Protein LigasesAnimalsFemaleHumansMiceMice, Inbred MRL lprProteinuriaUbiquitinationHistonesUbiquitin-Protein LigasesWWP2 protein, humanWwp2 protein, mouseH2Alupus nephritispodocyte injuryubiquitylationWWP2

Identifiers

PMID42694969
PMCPMC13540443

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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 OpenQuestion graph.