ArticleGastroenterology2009
Ethanol exposure depletes hepatic pigment epithelium-derived factor, a novel lipid regulator.
Article in Gastroenterology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Pigment Epithelial-Derived Factor Deficiency Accelerates Atherosclerosis Development via Promoting Endothelial Fatty Acid Uptake in Mice With Hyperlipidemia.Journal of the American Heart Association · 2019Article
- The effects of pigment epithelium-derived factor on atherosclerosis: putative mechanisms of the process.Lipids in health and disease · 2018Review
- Pigment Epithelium-Derived Factor Plays a Role in Alzheimer's Disease by Negatively Regulating Aβ42.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2018Article
- Pigment epithelium-derived factor in lipid metabolic disorders.Biomedical journal · 2018Review
- Pigment epithelium-derived factor, a noninhibitory serine protease inhibitor, is renoprotective by inhibiting the Wnt pathway.Kidney international · 2017Article
- Pigment Epithelium-derived Factor (PEDF) Blocks Wnt3a Protein-induced Autophagy in Pancreatic Intraepithelial Neoplasms.The Journal of biological chemistry · 2016Article
- Pigment epithelium-derived factor restoration increases bone mass and improves bone plasticity in a model of osteogenesis imperfecta type VI via Wnt3a blockade.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Pigment Epithelium Derived Factor Peptide Protects Murine Hepatocytes from Carbon Tetrachloride-Induced Injury.PloS one · 2016Article
- Pigment Epithelium-Derived Factor (PEDF) Inhibits Wnt/Cellular and molecular gastroenterology and hepatology · 2015Article
- PEDF and its roles in physiological and pathological conditions: implication in diabetic and hypoxia-induced angiogenic diseases.Clinical science (London, England : 1979) · 2015Review
- Article
- Pigment epithelium-derived factor (PEDF) suppresses IL-1β-mediated c-Jun N-terminal kinase (JNK) activation to improve hepatocyte insulin signaling.Endocrinology · 2014Article
- Determination of mesenchymal stem cell fate by pigment epithelium-derived factor (PEDF) results in increased adiposity and reduced bone mineral content.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- The intrinsic PEDF is regulated by PPARγ in permanent focal cerebral ischemia of rat.Neurochemical research · 2012Article
- Pigment epithelium-derived factor regulates early pancreatic fibrotic responses and suppresses the profibrotic cytokine thrombospondin-1.The American journal of pathology · 2011Article
- The vacuolar-ATPase modulates matrix metalloproteinase isoforms in human pancreatic cancer.Laboratory investigation; a journal of technical methods and pathology · 2011Article
- ¹H and ³¹P NMR lipidome of ethanol-induced fatty liver.Alcoholism, clinical and experimental research · 2010Article
- Pigment epithelium-derived factor is an intrinsic antifibrosis factor targeting hepatic stellate cells.The American journal of pathology · 2010Article
- Pigment epithelium-derived factor inhibits lysosomal degradation of Bcl-xL and apoptosis in HepG2 cells.The American journal of pathology · 2010Article
- Alcoholic Steatosis in Different Strains of Rat: A Comparative Study.Journal of drug and alcohol researchArticle
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsEthanol abuse can lead to hepatic steatosis and evolve into cirrhosis and hepatocellular carcinoma. Pigment epithelium-derived factor (PEDF) is a multifunctional secreted glycoprotein that is expressed by hepatocytes. Proteomic, experimental, and clinical studies implicate PEDF's role in lipid regulation. Because matrix metalloproteinase (MMP)-2/9 activity regulates PEDF levels, we investigated whether PEDF degradation by MMPs has a permissive role in ethanol-induced hepatic steatosis.
methodsPEDF levels were examined in liver biopsy specimens from patients with ethanol-induced steatosis. Hepatic PEDF levels and MMP activity were assessed in 2 animal models of ethanol feeding (rats on an alcohol-containing liquid diet and mice given intragastric infusion of ethanol). The consequences of PEDF depletion in the liver were examined in PEDF-null mice.
resultsLiver biopsy samples from patients with ethanol-induced steatosis had reduced PEDF levels, compared with normal liver samples. Ethanol-fed animals had histologic steatosis and increased liver triglyceride content (P< .05), as well as reduced levels of hepatic PEDF and increased MMP-2/9 activity. Ethanol-exposed hepatic lysates degraded PEDF in a MMP-2/9-dependent manner, and liver sections demonstrated abundant MMP-2/9 activity in situ. Addition of recombinant PEDF to PEDF-null hepatocytes, reduced their triglyceride content.
conclusionsEthanol exposure leads to marked loss of hepatic PEDF in human livers and in 2 animal models of ethanol feeding. Loss of PEDF contributes to the accumulation of lipids in ethanol-induced hepatic steatosis.
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Registered trials
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