ArticleEBioMedicine2021
Conjugated secondary 12α-hydroxylated bile acids promote liver fibrogenesis.
Article in EBioMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 105 citations in OpenAlex.
- Metabolic drivers of MASLD and MASH: from hormonal imbalance to fibrosis.Diabetologia · 2026Review
- Contribution of p38 MAPK in liver fibrosis: An overview of mechanisms, signaling pathways, and therapeutic targets (Review).International journal of molecular medicine · 2026Review
- Resveratrol Alleviates Arsenic-Induced Liver Fibrosis in Rats by Correcting SIRT1-Mediated Disorder of Hepatic Bile Acid Metabolism.International journal of molecular sciences · 2026Article
- Role of the gut microbiota-bile acid axis in liver fibrosis based on microbiomics and targeted metabolomics.BMC microbiology · 2026Article
- Integrated Omics Analysis of the Effects of Nano-Antimicrobial Peptide on the Intestinal Microbiota and Metabolome of Tibetan Sheep.Animals : an open access journal from MDPI · 2026Article
- The Conjugated Bile Acids Profile Suggests a Novel Liver-Muscle Axis Associated With Sarcopenia in Chronic Liver Disease.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- A metabolite-augmented FIB-4 machine learning panel achieves superior liver fibrosis staging in chronic liver disease.Cell reports. Medicine · 2026Article
- The role of bile acid dynamics in inflammatory bowel disease and metabolic dysfunction-associated steatotic liver disease.Liver research (Beijing, China) · 2026Review
- Mechanisms Underlying the Attenuating Effects of Bugantang on Liver Fibrosis Based on Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.Current computer-aided drug design · 2026Article
- Gut microbial bile salt hydrolase as a metabolic gatekeeper in digestive homeostasis and disease.Frontiers in immunology · 2026Review
- TMEM39A acts as a novel profibrotic factor to activate hepatic stellate cells partially via the cell adhesion molecule signaling axis.Frontiers in cell and developmental biology · 2026Article
- The role of bile acid-activated receptor TGR5 in inflammation and liver diseases.Frontiers in physiology · 2026Review
- The bile acid-gut microbiota-vitamin D axis: new insights into biliary atresia.Frontiers in cellular and infection microbiology · 2026Review
- Lithocholic Acid Species: Metabolism, Signaling Pathways, and Clinical Significance in Enterohepatic Diseases.International journal of molecular sciences · 2025Review
- Regulatory effects of Sini-San on bile acid homeostasis in the enterohepatic circulation of mice with liver fibrosis.Chinese medicine · 2025Article
- Conjugated bile acids in serum reflect disease severity and predict survival in chronic liver disease of humans and rats.Scientific reports · 2025Article
- Role of NLRP3 in the metabolism of bile acids and gut microbiota in CCl4-induced liver fibrosis.Microbiology spectrum · 2025Article
- Taurochenodeoxycholic acid as a sensitive stratification marker for HBV-associated hepatic cirrhosis status has a hepatoprotective effect.Scientific reports · 2025Article
- Differential roles of individual bile acid in physiology and disease.Pharmacological research · 2025Review
- Multifaceted Interactions Between Bile Acids, Their Receptors, and MASH: From Molecular Mechanisms to Clinical Therapeutics.Molecules (Basel, Switzerland) · 2025Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 10 institutions in 3 countries.
Funding
Abstract
backgroundSignificantly elevated serum and hepatic bile acid (BA) concentrations have been known to occur in patients with liver fibrosis. However, the roles of different BA species in liver fibrogenesis are not fully understood.
methodsWe quantitatively measured blood BA concentrations in nonalcoholic steatohepatitis (NASH) patients with liver fibrosis and healthy controls. We characterized BA composition in three mouse models induced by carbon tetrachloride (CCl
findingsWe found that a group of conjugated 12α-hydroxylated (12α-OH) BAs, such as taurodeoxycholate (TDCA) and glycodeoxycholate (GDCA), significantly increased in NASH patients and liver fibrosis mouse models. 12α-OH BAs significantly increased HSC proliferation and protein expression of fibrosis-related markers. Administration of TDCA and GDCA directly activated HSCs and promoted liver fibrogenesis in mouse models. Blockade of BA binding to TGR5 or inhibition of ERK1/2 and p38 MAPK signaling both significantly attenuated the BA-induced fibrogenesis. Liver fibrosis was attenuated in mice with Tgr5 depletion.
interpretationIncreased hepatic concentrations of conjugated 12α-OH BAs significantly contributed to liver fibrosis via TGR5 mediated p38MAPK and ERK1/2 signaling. Strategies to antagonize TGR5 or inhibit ERK1/2 and p38 MAPK signaling may effectively prevent or reverse liver fibrosis. FUNDINGS: This study was supported by the National Institutes of Health/National Cancer Institute Grant 1U01CA188387-01A1, the National Key Research and Development Program of China (2017YFC0906800); the State Key Program of National Natural Science Foundation (81430062); the National Natural Science Foundation of China (81974073, 81774196), China Postdoctoral Science Foundation funded project, China (2016T90381), and E-institutes of Shanghai Municipal Education Commission, China (E03008).
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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.