Leptin represses matrix metalloproteinase-1 gene expression in LX2 human hepatic stellate cells.

Leptin represses matrix metalloproteinase-1 gene expression in LX2 human hepatic stellate cells. Research Abstract Details 

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Leptin represses matrix metalloproteinase-1 gene expression in LX2 human hepatic stellate cells. Abstract Text:

Qi Cao,Ki M Mak,Charles S Lieber,

BACKGROUND/AIMS: Collagen accumulation in liver fibrosis is due in part to decreased expression of matrix metalloproteinase (MMP)-1 relative to TIMP-1. LX-2 hepatic stellate cells produce increased amounts of collagen and tissue inhibitor of metalloproteinase (TIMP)-1 in response to leptin. The effect of leptin on MMP-1 production has not been reported. METHODS: LX-2 cells were treated with leptin with or without inhibitors. We determined: phosphorylation of Janus kinase (JAK) 1 and -2, signal transducer and activator of transcription (STAT)3 and -5, extracellular signal-regulated kinase (ERK)1/2 and p38 by Western blot; H2O2 concentration by a colorimetric method; MMP-1 mRNA levels and stability by Northern blot; MMP-1 promoter activity as well as pro-MMP-1 by ELISA; and active MMP-1 by fluorescence. RESULTS: LX-2 cells constitutively expressed the MMP-1 gene and leptin repressed the basal level of MMP-1 mRNA and its promoter activity. The repression was mediated by JAK/STAT pathway in synergism with JAK-mediated H2O2-dependent ERK1/2 and p38 pathways. ERK1/2 inhibited MMP-1 promoter activity, whereas p38 decreased the message stability, contributing to mRNA down-regulation. Inhibition of MMP-1 gene diminished secreted pro-MMP-1 and active MMP-1. CONCLUSIONS: Leptin represses MMP-1 gene expression via the synergistic actions of the JAK/STAT pathway and JAK-mediated H2O2-dependent ERK1/2 and p38 pathways.

Leptin represses matrix metalloproteinase-1 gene expression in LX2 human hepatic stellate cells. Publishing Authors By Initials

Q Cao,KM Mak,CS Lieber,

For similar organic chemicals: hydrocarbons: hydrocarbons, cyclic: hydrocarbons, aromatic: benzene derivatives: benzylidene compounds: tyrphostins research abstracts see: organic chemicals: hydrocarbons: hydrocarbons, cyclic: hydrocarbons, aromatic: benzene derivatives: benzylidene compounds: tyrphostins research

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Leptin represses matrix metalloproteinase-1 gene expression in LX2 human hepatic stellate cells. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of hepatology

VOLUME: 46

Page Numbers: 124-33

Journal Abbreviation: J. Hepatol.

ISSN: 0168-8278

DAY: 22

MONTH: 09

YEAR: 2006

Leptin represses matrix metalloproteinase-1 gene expression in LX2 human hepatic stellate cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8503886

Leptin represses matrix metalloproteinase-1 gene expression in LX2 human hepatic stellate cells. Keywords Mesh Terms:

KEYWORDS: Tyrphostins

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Leptin represses matrix metalloproteinase-1 gene expression in LX2 human hepatic stellate cells. Information

Substance Name: Matrix Metalloproteinase 1

Registry Number: EC 3.4.24.7

Grant and Affiliation Information for Leptin represses matrix metalloproteinase-1 gene expression in LX2 human hepatic stellate cells.

AFFILIATION: Alcohol Research and Treatment Center, James J. Peters VA Medical Center, Bronx, and Mount Sinai School of Medicine, New York, NY 10029, USA.

Country: England

AGENCY: United States NIAAA

GRANT: AA11115

ACRONYM: AA

MEDLINETA: J Hepatol

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