ArticleProceedings of the National Academy of Sciences of the United States of America2018
RGMb protects against acute kidney injury by inhibiting tubular cell necroptosis via an MLKL-dependent mechanism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 96 citations in OpenAlex.
- Kidney‑enriched lipid nanoparticles delivering ANXA2 alleviate renal ischemia-reperfusion injury via CHMP2A-mediated necroptosis inhibition.Journal of nanobiotechnology · 2026Article
- Review
- Small molecules targeting regulated cell death for chronic kidney disease therapy.Journal of pharmaceutical analysis · 2026Review
- Targeting MLKL-Driven Necroptosis: A Therapeutic Target in Inflammation and Host Defense.Biomolecules · 2026Review
- Cross-talk among novel programmed cell death pathways: a decisive network in renal ischemia-reperfusion injury.Frontiers in immunology · 2026Review
- Mixed Lineage Kinase Domain-Like Protein (MLKL): From Mechanisms to Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Apoptosis, ferroptosis, necrosis, necroptosis and pyroptosis in the formation of calcium oxalate kidney stones.Urolithiasis · 2025Review
- Hippo pathway controls biopterin metabolism to shield adjacent cells from ferroptosis in lung cancer.EMBO reports · 2025Article
- Article
- Mechanisms of Acute Kidney Injury-Chronic Kidney Disease Transition: Unraveling Maladaptive Repair and Therapeutic Opportunities.Biomolecules · 2025Review
- RGMb drives macrophage infiltration to aggravate kidney disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- TEAD1 Prevents Necroptosis and Inflammation in Cisplatin-Induced Acute Kidney Injury Through Maintaining Mitochondrial Function.International journal of biological sciences · 2025Article
- Clinical-transcriptional prioritization of the circulating proteome in human heart failure.Cell reports. Medicine · 2024Article
- Inhibitors identify an auxiliary role for mTOR signalling in necroptosis execution downstream of MLKL activation.The Biochemical journal · 2024Article
- Renal tubular epithelial cells response to injury in acute kidney injury.EBioMedicine · 2024Review
- Blockage of Akt activation suppresses cadmium-induced renal tubular cellular damages through aggrephagy in HK-2 cells.Scientific reports · 2024Article
- The emerging role of regulated cell death in ischemia and reperfusion-induced acute kidney injury: current evidence and future perspectives.Cell death discovery · 2024Review
- Activation of the YAP/KLF5 transcriptional cascade in renal tubular cells aggravates kidney injury.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Connexin32 gap junction channels deliver miR155-3p to mediate pyroptosis in renal ischemia-reperfusion injury.Cell communication and signaling : CCS · 2024Article
- Ferroptosis in kidney disease: a bibliometric analysis from 2012 to 2024.Frontiers in pharmacology · 2024Review
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Authors and funding
18 authors at 8 institutions in 3 countries.
Funding
Abstract
Tubular cell necrosis is a key histological feature of acute kidney injury (AKI). Necroptosis is a type of programed necrosis, which is executed by mixed lineage kinase domain-like protein (MLKL) upon its binding to the plasma membrane. Emerging evidence indicates that necroptosis plays a critical role in the development of AKI. However, it is unclear whether renal tubular cells undergo necroptosis in vivo and how the necroptotic pathway is regulated during AKI. Repulsive guidance molecule (RGM)-b is a member of the RGM family. Our previous study demonstrated that RGMb is highly expressed in kidney tubular epithelial cells, but its biological role in the kidney has not been well characterized. In the present study, we found that RGMb reduced membrane-associated MLKL levels and inhibited necroptosis in cultured cells. During ischemia/reperfusion injury (IRI) or oxalate nephropathy, MLKL was induced to express on the apical membrane of proximal tubular (PT) cells. Specific knockout of Rgmb in tubular cells (Rgmb cKO) increased MLKL expression at the apical membrane of PT cells and induced more tubular cell death and more severe renal dysfunction compared with wild-type mice. Treatment with the necroptosis inhibitor Necrostatin-1 or GSK'963 reduced MLKL expression on the apical membrane of PT cells and ameliorated renal function impairment after IRI in both wild-type and Rgmb cKO mice. Taken together, our results suggest that proximal tubular cell necroptosis plays an important role in AKI, and that RGMb protects against AKI by inhibiting MLKL membrane association and necroptosis in proximal tubular cells.
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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.