ArticleCell death & disease2020
UCP2-induced hypoxia promotes lipid accumulation and tubulointerstitial fibrosis during ischemic kidney injury.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 52 citations in OpenAlex.
- Association of Nuclear Receptor Coactivators with Hypoxia-Inducible Factor-1BioMed research international · 2020Trial
- Imbalance of mitochondria and abnormalities in lipid metabolism in Diabetic Tubulopathy.Annals of medicine · 2026Review
- Bioadaptive spatiotemporal nanomedicine promotes metabolic recovery after myocardial infarction through NADNature cardiovascular research · 2026Article
- Reduced Cerebral Infarct Volume in Young UCP2Cells · 2026Article
- Fatty acid metabolism: opportunities and challenges of traditional Chinese medicine in the treatment of renal fibrosis.Chinese medicine · 2026Review
- UCP2 Upregulates ACSL3 to Enhance Lipid Droplet Release from Acinar Cells and Modulates the Sirt1/Smad3 Pathway to Promote Macrophage-to-Myofibroblast Transition in Chronic Pancreatitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- FTZ alleviates lipid deposition in diabetic kidney disease by AMPK/ACC/SREBP signaling pathway.Acta diabetologica · 2025Article
- SIRT3 regulates CPT1a acetylation and fatty acid oxidation in renal tubular epithelial cells under diabetic condition.Molecular biology reports · 2025Article
- Kidney lipid metabolism: impact on pediatric kidney diseases and modulation by early-life nutrition.Pediatric nephrology (Berlin, Germany) · 2025Review
- Emerging role and the signaling pathways of uncoupling protein 2 in kidney diseases.Renal failure · 2024Review
- Obeticholic acid ameliorates sepsis-induced renal mitochondrial damage by inhibiting the NF-κb signaling pathway.Renal failure · 2024Article
- Up-regulation of long non-coding RNA H19 ameliorates renal tubulointerstitial fibrosis by reducing lipid deposition and inflammatory response through regulation of the microRNA-130a-3p/long-chain acyl-CoA synthetase 1 axis.Non-coding RNA research · 2024Article
- Lipid nephrotoxicity mediated by HIF-1α activation accelerates tubular injury in diabetic nephropathy.Renal failure · 2024Article
- The role of uncoupling protein 2 in experimental periodontitis-associated renal injury in rats.Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2024Article
- [HIF-1α activation induces cholesterol homeostasis dysfunction to accelerate progression of diabetic nephropathy in rats].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- An international Delphi consensus statement on metabolic dysfunction-associated fatty liver disease and risk of chronic kidney disease.Hepatobiliary surgery and nutrition · 2023Review
- Importance of Mitochondria in Cardiac Pathologies: Focus on Uncoupling Proteins and Monoamine Oxidases.International journal of molecular sciences · 2023Review
- Proteomic profiling of IgA nephropathy reveals distinct molecular prognostic subtypes.iScience · 2023Article
- Mitochondrial Energy Metabolism in the Regulation of Thermogenic Brown Fats and Human Metabolic Diseases.International journal of molecular sciences · 2023Review
- Hypoxia-Inducible Factor 1 and Mitochondria: An Intimate Connection.Biomolecules · 2022Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial dysfunction leads to loss of renal function and structure; however, the precise mechanisms by which mitochondrial function can regulate renal fibrosis remain unclear. Proximal tubular cells (PTCs) prefer fatty acid oxidation as their energy source and dysregulation of lipid metabolism has been linked to tubulointerstitial fibrosis (TIF). Here, we demonstrated that mitochondrial uncoupling protein 2 (UCP2) regulates TIF through the stimulation of lipid deposition and extracellular matrix (ECM) accumulation. We show that UCP2 expression was increased in human biopsy sample and mouse kidney tissues with TIF. Moreover, UCP2-deficient mice displayed mitigated renal fibrosis in I/R-induced mouse model of TIF. Consistent with these results, UCP2 deficiency displayed reduced lipid deposition and ECM accumulation in vivo and in vitro. In UCP2-deficient PTCs, inhibition of TIF resulted from downregulation of hypoxia-inducible factor-1α (HIF-1α), a key regulator of lipid metabolism and ECM accumulation. Furthermore, we describe a molecular mechanism by which UCP2 regulates HIF-1α stabilization through regulation of mitochondrial respiration and tissue hypoxia during TIF. HIF-1α inhibition by siRNA suppressed lipid and ECM accumulation by restoration of PPARα and CPT1α, as well as suppression of fibronectin and collagen I expression in PTCs. In conclusion, our results suggest that UCP2 regulates TIF by inducing the HIF-1α stabilization pathway in tubular cells. These results identify UCP2 as a potential therapeutic target in treating chronic renal fibrosis.
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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.