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J Hepatol. 2007 Jan;46(1):124-33. Epub 2006 Sep 22.

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

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  • 1Alcohol Research and Treatment Center, James J. Peters VA Medical Center, Bronx, and Mount Sinai School of Medicine, New York, NY 10029, USA.



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.


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.


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.


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.

[PubMed - indexed for MEDLINE]
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