1
40
1
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1074/jbc.M109.022244" target="_blank" rel="noreferrer noopener">http://doi.org/10.1074/jbc.M109.022244</a>
Rights
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Pages
28510-28521
Issue
42
Volume
284
Search for Full-text
Locate full-text within NEOMED Library's e-journal collections
<p>Users with a NEOMED Library login can search for full-text journal articles at the following url: <a href="https://libraryguides.neomed.edu/home">https://libraryguides.neomed.edu/home</a></p>
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Hepatocyte Growth Factor Family Negatively Regulates Hepatic Gluconeogenesis via Induction of Orphan Nuclear Receptor Small Heterodimer Partner in Primary Hepatocytes
Publisher
An entity responsible for making the resource available
Journal of Biological Chemistry
Date
A point or period of time associated with an event in the lifecycle of the resource
2009
2009-10
Subject
The topic of the resource
signaling pathway; mice; hyperglycemia; Biochemistry & Molecular Biology; gene-expression; promoter; activated protein-kinase; insulin; diabetic-nephropathy; hepg2 liver-cells; upstream
Creator
An entity primarily responsible for making the resource
Chanda D; Li T G; Song K H; Kim Y H; Sim J G; Lee C H; Chiang J Y L; Choi H S
Description
An account of the resource
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 4 alpha-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.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1074/jbc.M109.022244" target="_blank" rel="noreferrer noopener">10.1074/jbc.M109.022244</a>
Format
The file format, physical medium, or dimensions of the resource
Journal Article or Conference Abstract Publication
2009
activated protein-kinase
Biochemistry & Molecular Biology
Chanda D
Chiang J Y L
Choi H S
diabetic-nephropathy
gene-expression
hepg2 liver-cells
hyperglycemia
insulin
Journal Article or Conference Abstract Publication
Journal of Biological Chemistry
Kim Y H
Lee C H
Li T G
Mice
promoter
signaling pathway
Sim J G
Song K H
upstream