ArticleThe Journal of clinical investigation2018
iRhom2 promotes lupus nephritis through TNF-α and EGFR signaling.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 97 citations in OpenAlex.
- Congenital iRHOM2 deficiency causes ADAM17 dysfunction and environmentally directed immunodysregulatory disease.Nature immunology · 2022Trial
- Targeting iRhom2-mediated PANoptosis ameliorates acute kidney injury.Acta pharmacologica Sinica · 2026Article
- Serum Soluble Mediator Signatures of Lupus Nephritis: Histologic Features and Response to Treatment.Arthritis care & research · 2026Article
- An additional site mutation in MITA/STING gain-of-function mutants abolishes the autoimmune SAVI phenotypes and directs a therapeutic strategy.Cell insight · 2026Article
- iRhom2 regulates HMGB1 secretion to modulate inflammation and hepatocyte senescence in an in vitro model of ischemia-reperfusion injury.Cell death & disease · 2026Article
- miR-7213-5p-mediated suppression of CCL19 in fibroblast cells may attenuate lupus nephritis.Clinical and experimental medicine · 2025Article
- Holding Out for a Model: Rhomboid Superfamily in Vertebrate Development and Disease.Journal of cellular physiology · 2025Review
- Combined Network Pharmacology, Transcriptomics and Metabolomics Strategies Reveal the Mechanism of Action of Lang Chuang Wan to Ameliorate Lupus Nephritis in MRL/lpr Mice.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Structural insights into the activation and inhibition of the ADAM17-iRhom2 complex.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Engineered macrophage membrane-coated dihydroartemisinin nanoparticles with enhanced CCR2 expression improved symptoms in MRL/LPR mice by metabolic reprogramming of proinflammatory macrophages.Journal of translational medicine · 2025Article
- Soluble urine activated leukocyte cell adhesion molecule is a strong predictor of lupus nephritis.Rheumatology (Oxford, England) · 2025Article
- The late-onset Alzheimer's disease risk factor RHBDF2 is a modifier of microglial TREM2 proteolysis.Life science alliance · 2025Article
- iRhom2 deficiency reduces sepsis-induced mortality associated with the attenuation of lung macrophages in mice.Histochemistry and cell biology · 2024Article
- The interferon-rich skin environment regulates Langerhans cell ADAM17 to promote photosensitivity in lupus.eLife · 2024Article
- Targeting the epidermal growth factor receptor (EGFR/ErbB) for the potential treatment of renal pathologies.Frontiers in pharmacology · 2024Review
- Epidermal growth factor receptor activation is essential for kidney fibrosis development.Nature communications · 2023Article
- Analysis of the function of ADAM17 in iRhom2 curly-bare and tylosis with esophageal cancer mutant mice.Journal of cell science · 2023Article
- RHBDF2 is correlated with immune infiltrates in hepatocellular carcinoma and may have potential as a biomarker.FEBS open bio · 2023Article
- The ADAM17 sheddase complex regulator iTAP/Frmd8 modulates inflammation and tumor growth.Life science alliance · 2023Article
- Exploring the potential mechanisms of Shiwei Hezi pill against nephritis based on the method of network pharmacology.Frontiers in pharmacology · 2023Article
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12 authors at 6 institutions in 4 countries.
Funding
Abstract
Lupus nephritis (LN) often results in progressive renal dysfunction. The inactive rhomboid 2 (iRhom2) is a newly identified key regulator of A disintegrin and metalloprotease 17 (ADAM17), whose substrates, such as TNF-α and heparin-binding EGF (HB-EGF), have been implicated in the pathogenesis of chronic kidney diseases. Here, we demonstrate that deficiency of iRhom2 protects the lupus-prone Fcgr2b-/- mice from developing severe kidney damage without altering anti-double-stranded DNA (anti-dsDNA) Ab production by simultaneously blocking HB-EGF/EGFR and TNF-α signaling in the kidney tissues. Unbiased transcriptome profiling of kidneys and kidney macrophages revealed that TNF-α and HB-EGF/EGFR signaling pathways are highly upregulated in Fcgr2b-/- mice, alterations that were diminished in the absence of iRhom2. Pharmacological blockade of either TNF-α or EGFR signaling protected Fcgr2b-/- mice from severe renal damage. Finally, kidneys from LN patients showed increased iRhom2 and HB-EGF expression, with interstitial HB-EGF expression significantly associated with chronicity indices. Our data suggest that activation of iRhom2/ADAM17-dependent TNF-α and EGFR signaling plays a crucial role in mediating irreversible kidney damage in LN, thereby uncovering a target for selective and simultaneous dual inhibition of 2 major pathological pathways in the effector arm of the disease.
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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.