ArticleHepatology (Baltimore, Md.)2022
E3 ubiquitin ligase ring finger protein 5 protects against hepatic ischemia reperfusion injury by mediating phosphoglycerate mutase family member 5 ubiquitination.
Article in Hepatology (Baltimore, Md.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 66 citations in OpenAlex.
- RNF5 promotes acute lung injury through HSPA5 ER-to-cytosol translocation and resultant PERK activation.Cell death and differentiation · 2026Article
- GADD45B promotes apoptosis in intestinal ischemia/reperfusion through DNA demethylation of MST1/Hippo.Chinese medical journal · 2026Article
- Protective effect of Caftaric Acid against hepatic cold ischemia/reperfusion injury in the liver.Biology direct · 2026Article
- Umbilical cord mesenchymal stromal cells-derived HGF inhibits STING-mediated pyroptosis to alleviate cerebral ischemia/reperfusion injury via c-Met/β-catenin/RNF5 pathway.Journal of translational medicine · 2026Article
- Mild hypothermia attenuates hepatic ischemia-reperfusion injury by regulating FoxO1/PPARα pathway.Scientific reports · 2025Article
- Nuclear receptor FXR inhibits ferroptosis to alleviate hepatic ischemia-reperfusion injury by targeting GPX4 in a mouse model.Journal of molecular histology · 2025Article
- A simplified and reproducibleLiver research (Beijing, China) · 2025Article
- Pharmacological inhibition of ENaC or NCX can attenuate hepatic ischemia-reperfusion injury exacerbated by hypernatremia.Journal of Zhejiang University. Science. B · 2025Article
- Lactylation: a promising therapeutic target in ischemia-reperfusion injury management.Cell death discovery · 2025Review
- Review
- The dual role of PGAM5 in inflammation.Experimental & molecular medicine · 2025Review
- Disruption of tumor-intrinsic PGAM5 increases anti-PD-1 efficacy through the CCL2 signaling pathway.Journal for immunotherapy of cancer · 2025Article
- PGAM5 Modulates Macrophage Polarization, Aggravating Inflammation in COPD via the NF-κB Pathway.International journal of chronic obstructive pulmonary disease · 2025Article
- Activated AXL Ameliorates Alcohol-associated Steatotic Liver Ischemia-Reperfusion Injury by Inhibiting ER stress and Mitochondria-associated Apoptosis.International journal of biological sciences · 2025Article
- Protein modifications in hepatic ischemia-reperfusion injury: molecular mechanisms and targeted therapy.Frontiers in immunology · 2025Review
- Current status and perspective on molecular targets and therapeutic intervention strategy in hepatic ischemia-reperfusion injury.Clinical and molecular hepatology · 2024Review
- RING finger protein 5 protects against acute myocardial infarction by inhibiting ASK1.BMC cardiovascular disorders · 2024Article
- Phosphoglycerate mutase 5 exacerbates liver ischemia-reperfusion injury by activating mitochondrial fission.Scientific reports · 2024Article
- 6-Gingerol attenuates hepatic ischemia/reperfusion injury through regulating MKP5-mediated P38/JNK pathway.Scientific reports · 2024Article
- Lactobacillus reuteri mitigates hepatic ischemia/reperfusion injury by modulating gut microbiota and metabolism through the Nrf2/HO-1 signaling.Biology direct · 2024Article
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Authors and funding
21 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsHepatic ischemia-reperfusion (HIR) injury, a common clinical complication of liver transplantation and resection, affects patient prognosis. Ring finger protein 5 (RNF5) is an E3 ubiquitin ligase that plays important roles in endoplasmic reticulum stress, unfolded protein reactions, and inflammatory responses; however, its role in HIR is unclear. APPROACH AND
resultsRNF5 expression was significantly down-regulated during HIR in mice and hepatocytes. Subsequently, RNF5 knockdown and overexpression of cell lines were subjected to hypoxia-reoxygenation challenge. Results showed that RNF5 knockdown significantly increased hepatocyte inflammation and apoptosis, whereas RNF5 overexpression had the opposite effect. Furthermore, hepatocyte-specific RNF5 knockout and transgenic mice were established and subjected to HIR, and RNF5 deficiency markedly aggravated liver damage and cell apoptosis and activated hepatic inflammatory responses, whereas hepatic RNF5 transgenic mice had the opposite effect compared with RNF5 knockout mice. Mechanistically, RNF5 interacted with phosphoglycerate mutase family member 5 (PGAM5) and mediated the degradation of PGAM5 through K48-linked ubiquitination, thereby inhibiting the activation of apoptosis-regulating kinase 1 (ASK1) and its downstream c-Jun N-terminal kinase (JNK)/p38. This eventually suppresses the inflammatory response and cell apoptosis in HIR.
conclusionsWe revealed that RNF5 protected against HIR through its interaction with PGAM5 to inhibit the activation of ASK1 and the downstream JNK/p38 signaling cascade. Our findings indicate that the RNF5-PGAM5 axis may be a promising therapeutic target for HIR.
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