ArticleThe Journal of biological chemistry2007
Activation of bile acid biosynthesis by the p38 mitogen-activated protein kinase (MAPK): hepatocyte nuclear factor-4alpha phosphorylation by the p38 MAPK is required for cholesterol 7alpha-hydroxylase expression.
Article in The Journal of biological chemistry, 2007. 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, 47 citations in OpenAlex.
- Hepatocyte-Derived FGF1 Alleviates Isoniazid and Rifampicin-Induced Liver Injury by Regulating HNF4α-Mediated Bile Acids Synthesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Metabolic self-feeding in HBV-associated hepatocarcinoma centered on feedback between circulation lipids and the cellular MAPK/mTOR axis.Cell communication and signaling : CCS · 2024Article
- Mitogen-Activated Protein Kinase and Exploratory Nuclear Receptor Crosstalk in Cancer Immunotherapy.International journal of molecular sciences · 2023Review
- Pharmacologic inhibition of HNF4α prevents parenteral nutrition associated cholestasis in mice.Scientific reports · 2023Article
- Cellular Location of HNF4α is Linked With Terminal Liver Failure in Humans.Hepatology communications · 2020Article
- StarD5: an ER stress protein regulates plasma membrane and intracellular cholesterol homeostasis.Journal of lipid research · 2019Article
- The transcriptional activity of hepatocyte nuclear factor 4 alpha is inhibited via phosphorylation by ERK1/2.PloS one · 2017Article
- Murine model of long-term obstructive jaundice.The Journal of surgical research · 2016Article
- Crosstalk of HNF4Acta pharmaceutica Sinica. B · 2016Review
- p38 MAPK α and β isoforms differentially regulate plasma membrane localization of MRP2.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- ROCK inhibition enhances microRNA function by promoting deadenylation of targeted mRNAs via increasing PAIP2 expression.Nucleic acids research · 2015Article
- Promotion of hepatic differentiation of bone marrow mesenchymal stem cells on decellularized cell-deposited extracellular matrix.BioMed research international · 2013Article
- Mechanism of tissue-specific farnesoid X receptor in suppressing the expression of genes in bile-acid synthesis in mice.Hepatology (Baltimore, Md.) · 2012Article
- INTRACELLULAR SIGNALING BY BILE ACIDS.Journal of bio-science · 2012Article
- Ligand-dependent regulation of the activity of the orphan nuclear receptor, small heterodimer partner (SHP), in the repression of bile acid biosynthetic CYP7A1 and CYP8B1 genes.Molecular endocrinology (Baltimore, Md.) · 2011Article
- Proteomic analysis of native hepatocyte nuclear factor-4α (HNF4α) isoforms, phosphorylation status, and interactive cofactors.The Journal of biological chemistry · 2011Article
- Cyclic AMP stimulates Mrp2 translocation by activating p38{alpha} MAPK in hepatic cells.American journal of physiology. Gastrointestinal and liver physiology · 2010Article
- α(1)-Fetoprotein Transcription Factor (FTF)/Liver Receptor Homolog-1 (LRH-1) Is an Essential Lipogenic Regulator.Biochimica et biophysica acta · 2010Article
- Tissue-specific activation of mitogen-activated protein kinases for expression of transthyretin by phenylalanine and its metabolite, phenylpyruvic acid.Experimental & molecular medicine · 2010Article
- Bile acid signaling pathways increase stability of Small Heterodimer Partner (SHP) by inhibiting ubiquitin-proteasomal degradation.Genes & development · 2009Article
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9 authors at 1 institution in 1 country.
Funding
Abstract
Bile acids are required for intestinal absorption and biliary solubilization of cholesterol and lipids. In addition, bile acids play a crucial role in cholesterol homeostasis. One of the key enzymes in the bile acid biosynthetic pathways is cholesterol 7alpha-hydroxylase/cytochrome P450 7alpha-hydroxylase (7alpha-hydroxylase), which is the rate-limiting and regulatory step of the "classic" pathway. Transcription of the 7alpha-hydroxylase gene is highly regulated. Two nuclear receptors, hepatocyte nuclear factor 4alpha (HNF-4alpha) and alpha(1)-fetoprotein transcription factor, are required for both transcription and regulation by different physiological events. It has been shown that some mitogen-activated protein kinases, such as the c-Jun N-terminal kinase and the ERK, play important roles in the regulation of 7alpha-hydroxylase transcription. In this study, we show evidence that the p38 kinase pathway plays an important role in 7alpha-hydroxylase expression and hence in bile acid synthesis. Inhibition of p38 kinase activity in primary hepatocytes results in approximately 5-10-fold reduction of 7alpha-hydroxylase mRNA. This suppression is mediated, at least in part, through HNF-4alpha. Inhibition of p38 kinase activity diminishes HNF-4alpha nuclear protein levels and its phosphorylation in vivo and in vitro, and it renders a less stable protein. Induction of the p38 kinase pathway by insulin results in an increase in HNF-4alpha protein and a concomitant induction of 7alpha-hydroxylase expression that is blocked by inhibiting the p38 pathway. These studies show a functional link between the p38 signaling pathway, HNF-4alpha, and bile acid synthesis.
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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.