ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2014
Prolonged exposure of cholestatic rats to complete dark inhibits biliary hyperplasia and liver fibrosis.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Elevated diurnal CD36 expression disrupts the bile acid synthesis rhythm leading to cholestatic liver injury and inflammation via the HMGCR/CYP7A1 axis.Genes & diseases · 2026Article
- Parenteral nutrition results in peripheral ileal to hepatic circadian discordance in mice.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Chronobiology of Cancers in the Liver and Gut.Cancers · 2024Review
- Article
- Circadian clock core component Bmal1 dictates cell cycle rhythm of proliferating hepatocytes during liver regeneration.American journal of physiology. Gastrointestinal and liver physiology · 2021Article
- Melatonin Protects Cholangiocytes from Oxidative Stress-Induced Proapoptotic and Proinflammatory Stimuli via miR-132 and miR-34.International journal of molecular sciences · 2020Article
- Melatonin and circadian rhythms in liver diseases: Functional roles and potential therapies.Journal of pineal research · 2020Review
- Possible application of melatonin treatment in human diseases of the biliary tract.American journal of physiology. Gastrointestinal and liver physiology · 2019Review
- Knockdown of vimentin reduces mesenchymal phenotype of cholangiocytes in the Mdr2EBioMedicine · 2019Article
- Circadian rhythms: a possible new player in non-alcoholic fatty liver disease pathophysiology.Journal of molecular medicine (Berlin, Germany) · 2019Review
- Pinealectomy or light exposure exacerbates biliary damage and liver fibrosis in cholestatic rats through decreased melatonin synthesis.Biochimica et biophysica acta. Molecular basis of disease · 2019Article
- Preclinical insights into cholangiopathies: disease modeling and emerging therapeutic targets.Expert opinion on therapeutic targets · 2019Review
- The Role of Autophagy in Liver Epithelial Cells and Its Impact on Systemic Homeostasis.Nutrients · 2019Review
- Epidermal growth factor-like domain multiple 7 (EGFL7): Expression and possible effect on biliary epithelium growth in cholangiocarcinoma.European journal of histochemistry : EJH · 2018Article
- Knockout of secretin receptor reduces biliary damage and liver fibrosis in Mdr2Laboratory investigation; a journal of technical methods and pathology · 2018Article
- Emerging role of circadian clock disruption in alcohol-induced liver disease.American journal of physiology. Gastrointestinal and liver physiology · 2018Review
- Biliary epithelium: A neuroendocrine compartment in cholestatic liver disease.Clinics and research in hepatology and gastroenterology · 2018Review
- Recent advances in understanding bile duct remodeling and fibrosis.F1000Research · 2018Review
- Melatonin inhibits hypothalamic gonadotropin-releasing hormone release and reduces biliary hyperplasia and fibrosis in cholestatic rats.American journal of physiology. Gastrointestinal and liver physiology · 2017Article
- Prolonged darkness reduces liver fibrosis in a mouse model of primary sclerosing cholangitis by miR-200b down-regulation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Biliary hyperplasia and liver fibrosis are common features in cholestatic liver disease. Melatonin is synthesized by the pineal gland as well as the liver. Melatonin inhibits biliary hyperplasia of bile duct-ligated (BDL) rats. Since melatonin synthesis (by the enzyme serotonin N-acetyltransferase, AANAT) from the pineal gland increases after dark exposure, we hypothesized that biliary hyperplasia and liver fibrosis are diminished by continuous darkness via increased melatonin synthesis from the pineal gland. Normal or BDL rats (immediately after surgery) were housed with light-dark cycles or complete dark for 1 wk before evaluation of 1) the expression of AANAT in the pineal gland and melatonin levels in pineal gland tissue supernatants and serum; 2) biliary proliferation and intrahepatic bile duct mass, liver histology, and serum chemistry; 3) secretin-stimulated ductal secretion (functional index of biliary growth); 4) collagen deposition, liver fibrosis markers in liver sections, total liver, and cholangiocytes; and 5) expression of clock genes in cholangiocytes. In BDL rats exposed to dark there was 1) enhanced AANAT expression/melatonin secretion in pineal gland and melatonin serum levels; 2) improved liver morphology, serum chemistry and decreased biliary proliferation and secretin-stimulated choleresis; and 4) decreased fibrosis and expression of fibrosis markers in liver sections, total liver and cholangiocytes and reduced biliary expression of the clock genes PER1, BMAL1, CLOCK, and Cry1. Thus prolonged dark exposure may be a beneficial noninvasive therapeutic approach for the management of biliary disorders.
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