ArticleCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology2018
Regulatory Role of Endothelial PHD2 in the Hepatic Steatosis.
Article in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 15 citations in OpenAlex.
- The role of liver sinusoidal endothelial cells in metabolic dysfunction-associated steatotic liver diseases and liver cancer: mechanisms and potential therapies.Angiogenesis · 2025Review
- Endothelial Cell-Specific Prolyl Hydroxylase-2 Deficiency Augments Angiotensin II-Induced Arterial Stiffness and Cardiac Pericyte Recruitment in Mice.Journal of the American Heart Association · 2024Article
- The glycolytic process in endothelial cells and its implications.Acta pharmacologica Sinica · 2022Review
- Role of liver sinusoidal endothelial cells in liver diseases.Nature reviews. Gastroenterology & hepatology · 2021Review
- Prediction of High-Altitude Cardiorespiratory Fitness Impairment Using a Combination of Physiological Parameters During Exercise at Sea Level and Genetic Information in an Integrated Risk Model.Frontiers in cardiovascular medicine · 2021Article
- Endothelial prolyl hydroxylase 2 is necessary for angiotensin II-mediated renal fibrosis and injury.American journal of physiology. Renal physiology · 2020Article
- Review
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND/
aimsLiver disease is a leading cause of high mortality and morbidity worldwide. The aim of the present study is to investigate the regulatory role of prolyl hydroxylase-2 (PHD2)-hypoxia-inducible factor-2a (HIF-2α) axis on nonalcoholic fatty liver disease (NAFLD) and to explore the potential mechanisms by which endothelial (EC)-specific PHD2 deficiency regulates hepatic steatosis and fibrosis.
methodsIn the endothelial-specific PHD2 knockout (PHD2ECKO) mouse fed with normal diet or high fat diet (HFD), liver lipid accumulation and fibrosis were measured by Oil Red O and Masson trichrome staining. The fat and body weight (FW/BW) ratio and glucose tolerance were measured. The expression of HIF-2α, atrial natriuretic peptide (ANP), angiopoietin-2 (Ang-2), and transforming growth factor-b (TGF-β) were analyzed by western blot analysis.
resultsThe steatosis and fibrosis were significantly increased in the PHD2ECKO mice. FW/BW ratio was significantly increased in the PHD2ECKO mice. Moreover, knockout of endothelial PHD2 resulted in an impairment of glucose tolerance in mice. Western blot analysis showed that the expression of HIF-2α in liver tissues was not significantly increased. Interestingly, the expression of ANP was decreased, and Ang-2 and TGF-β levels were significantly increased in the liver of PHD2ECKO mice. The FW/BW ratio was also significantly increased in the PHD2ECKO mice fed with HFD for 16 weeks. Feeding HFD resulted in a significant increase in hepatic steatosis in the control PHD2f/f mice, but did not further enhance hepatic steatosis in the PHD2ECKO mice.
conclusionsWe concluded that the endothelial PHD2 plays a critical role in hepatic steatosis and fibrosis, which may be involved in the regulation of ANP and Ang-2/TGF-β signaling pathway, but not the HIF-2α expression.
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