ArticleThe Journal of biological chemistry2009
Hepatocyte growth factor family negatively regulates hepatic gluconeogenesis via induction of orphan nuclear receptor small heterodimer partner in primary hepatocytes.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 55 citations in OpenAlex.
- De Novo Lipogenesis in Clear Cell Renal Cell Carcinoma: Mechanistic Insights and Therapeutic Implications.International journal of molecular sciences · 2026Review
- The role of hepatocyte growth factor in the relationship between body fat distribution and plasma markers of glucose metabolism: a cross-sectional study.Diabetology & metabolic syndrome · 2026Article
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- MSP-RON signaling in liver pathobiology and as an emerging therapeutic target: a review of the current evidence.Cell communication and signaling : CCS · 2025Review
- A network map of macrophage-stimulating protein (MSP) signaling.Journal of cell communication and signaling · 2023Article
- Quantitative Proteomic Analysis of Serum Reveals MST1 as a Potential Candidate Biomarker in Spontaneously Diabetic Cynomolgus Monkeys.ACS omega · 2022Article
- Vascular and Liver Homeostasis in Juvenile Mice Require Endothelial Cyclic AMP-Dependent Protein Kinase A.International journal of molecular sciences · 2022Article
- The role of AMPK-dependent pathways in cellular and molecular mechanisms of metformin: a new perspective for treatment and prevention of diseases.Inflammopharmacology · 2022Review
- MSP-RON Pathway: Potential Regulator of Inflammation and Innate Immunity.Frontiers in immunology · 2020Review
- Regulation of Energy Metabolism by Receptor Tyrosine Kinase Ligands.Frontiers in physiology · 2020Review
- Small heterodimer partner negatively regulates C-X-C motif chemokine ligand 2 in hepatocytes during liver inflammation.Scientific reports · 2018Article
- Nuclear Receptor SHP: A Critical Regulator of miRNA and lncRNA Expression and Function.Nuclear receptor research · 2017Article
- Orphan nuclear receptor SHP regulates iron metabolism through inhibition of BMP6-mediated hepcidin expression.Scientific reports · 2016Article
- MSP is a negative regulator of inflammation and lipogenesis in ex vivo models of non-alcoholic steatohepatitis.Experimental & molecular medicine · 2016Article
- Small Heterodimer Partner (NR0B2) Coordinates Nutrient Signaling and the Circadian Clock in Mice.Molecular endocrinology (Baltimore, Md.) · 2016Article
- Small Heterodimer Partner and Innate Immune Regulation.Endocrinology and metabolism (Seoul, Korea) · 2016Review
- Transcriptional regulation of hepatic lipogenesis.Nature reviews. Molecular cell biology · 2015Review
- Orphan nuclear receptor oestrogen-related receptor γ (ERRγ) plays a key role in hepatic cannabinoid receptor type 1-mediated induction of CYP7A1 gene expression.The Biochemical journal · 2015Article
- Salidroside ameliorates insulin resistance through activation of a mitochondria-associated AMPK/PI3K/Akt/GSK3β pathway.British journal of pharmacology · 2015Article
- Small heterodimer partner interacts with NLRP3 and negatively regulates activation of the NLRP3 inflammasome.Nature communications · 2015Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Hepatic gluconeogenesis is tightly balanced by opposing stimulatory (glucagon) and inhibitory (insulin) signaling pathways. Hepatocyte growth factor (HGF) is a pleiotropic growth factor that mediates diverse biological processes. In this study, we investigated the effect of HGF and its family member, macrophage-stimulating factor (MSP), on hepatic gluconeogenesis in primary hepatocytes. HGF and MSP significantly repressed expression of the key hepatic gluconeogenic enzyme genes, phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (Glc-6-Pase) and reduced glucose production. HGF and MSP activated small heterodimer partner (SHP) gene promoter and induced SHP mRNA and protein levels, and the effect of HGF and MSP on SHP gene expression was demonstrated to be mediated via activation of the AMP-activated protein kinase (AMPK) signaling pathway. We demonstrated that upstream stimulatory factor-1 (USF-1) specifically mediated HGF effect on SHP gene expression, and inhibition of USF-1 by dominant negative USF-1 significantly abrogated HGF-mediated activation of the SHP promoter. Elucidation of the mechanism showed that USF-1 bound to E-box-1 in the SHP promoter, and HGF increased USF-1 DNA binding on the SHP promoter via AMPK and DNA-dependent protein kinase-mediated pathways. Adenoviral overexpression of USF-1 significantly repressed PEPCK and Glc-6-Pase gene expression and reduced glucose production. Knockdown of endogenous SHP expression significantly reversed this effect. Finally, knockdown of SHP or inhibition of AMPK signaling reversed the ability of HGF to suppress hepatocyte nuclear factor 4alpha-mediated up-regulation of PEPCK and Glc-6-Pase gene expression along with the HGF- and MSP-mediated suppression of gluconeogenesis. Overall, our results suggest a novel signaling pathway through HGF/AMPK/USF-1/SHP to inhibit hepatic gluconeogenesis.
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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.