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Leptin Induces Increased α2(I) Collagen Gene Expression in Cultured Rat Hepatic Stellate Cells

Content Provider	PubMed Central
Author	Saxena, Neeraj K. Saliba, George Floyd, Jeffrey J. Anania, Frank A.
Copyright Year	2003
Abstract	Leptin is a 16-kDa hormone with an array of biologic actions. We, and others, have demonstrated that leptin is critical to the development of liver fibrogenesis both in vitro and in the lean littermates of ob/ob mice exposed to carbon tetrachloride (CCl4). Controversy exists as to whether leptin can act as a direct cytokine in the development of increased collagen expression, and whether ob/ob mice are resistant to potential injury from CCl4. Here, we provide evidence that strongly suggests that leptin acts to increase nascent production of mRNA for the α2(I) collagen gene based upon ribonuclease protection analysis (RPA). Actinomycin D, but not cyclohexamide, or the pan-neutralizing antibody to transforming growth factor beta one (TGFβ1), significantly diminished the effect of leptin on total α2(I) collagen mRNA levels. Further evidence that leptin acts directly on HSCs to alter gene expression in liver wounding is demonstrated by enhanced binding of phosphorylated signal transduction and activator of transcription factor 3 (pStat3) to a cis-inducible element (SIE) oligonucleotide by electrophoretic mobility shift assay (EMSA). This consensus sequence is responsible for production of a critical collagen transcription factor, AP-1. Finally, we have demonstrated from the ob/ob mouse model that these animals are at least as sensitive to CCl4 as their respective lean animals as assessed by serum alanine aminotransferase (ALT) measurements. Taken together, the current data provide a continued framework that leptin is a profibrogenic cytokine and plays a key role in liver fibrosis.
Related Links	http://dx.doi.org/10.1002/jcb.10494
Ending Page	320
Page Count	10
Starting Page	311
File Format	PDF
ISSN	07302312
e-ISSN	10974644
Journal	Journal of cellular biochemistry
Issue Number	2
Volume Number	89
Language	English
Publisher Date	2003-05-15
Access Restriction	Open
Subject Keyword	Cell Biology Biochemistry Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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