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PMID: 12223100 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Acetaldehyde stimulates the activation of latent transforming growth factor-beta1 and induces expression of the type II receptor of the cytokine in rat cultured hepatic stellate cells.

The Biochemical journal ·Vol. 368 ·No. Pt 3 ·2002-12-15 ·Pages 683-93

Chen A

Abstract

Acetaldehyde, the major active metabolite of alcohol, induces the activation of hepatic stellate cells (HSC), leading to over-production of alpha1(I) collagen and ultimately causing hepatic fibrosis. The underlying mechanisms of this process remain largely unknown. Transforming growth factor-beta1 (TGF-beta1) is a potent inducer of alpha1(I) collagen production. Accumulating evidence has shown a potential role for TGF-beta1 in alcohol-induced hepatic fibrogenesis. The aims of this study were to determine the effect of acetaldehyde on TGF-beta signalling, to elucidate the underlying mechanisms as well as to evaluate its role in expression of alpha1(I) collagen gene in cultured HSC. It was hypothesized that acetaldehyde activated TGF-beta signalling by inducing the expression of elements in the TGF-beta signal transduction pathway, which might contribute to alpha1(I) collagen gene expression in cultured HSC. Initial results revealed that acetaldehyde activated TGF-beta signalling in cultured HSC. Additional studies demonstrated that acetaldehyde stimulated the secretion and activation of latent TGF-beta1, and induced the expression of the type II TGF-beta receptor (Tbeta-RII). Further experiments found cis - and trans -activating elements responsible for Tbeta-RII gene expression induced by acetaldehyde. Activation of TGF-beta signalling by acetaldehyde contributed to alpha1(I) collagen gene expression in cultured HSC. In summary, this report demonstrated that acetaldehyde stimulated TGF-beta signalling by increasing the secretion and activation of latent TGF-beta1 as well as by inducing the expression of Tbeta-RII in cultured HSC. Results from this report provided a novel insight into mechanisms by which acetaldehyde stimulated the expression of alpha1(I) collagen in HSC and a better understanding of effects of alcohol (or acetaldehyde) on hepatic fibrogenesis.

MeSH Terms
Acetaldehyde/metabolism,pharmacology Alcohols/metabolism Animals Blotting, Western Cell Line Collagen/metabolism Culture Media, Serum-Free/pharmacology Dose-Response Relationship, Drug Enzyme-Linked Immunosorbent Assay Gene Expression Regulation Liver/cytology,metabolism Male Models, Biological Oligonucleotides, Antisense/pharmacology Plasmids/metabolism Promoter Regions, Genetic Protein Binding Protein Serine-Threonine Kinases RNA/metabolism Rats Rats, Sprague-Dawley Receptor, Transforming Growth Factor-beta Type II Receptors, Transforming Growth Factor beta/metabolism Ribonucleases/metabolism Signal Transduction Time Factors Transcriptional Activation Transfection Transforming Growth Factor beta/metabolism Transforming Growth Factor beta1 Up-Regulation
Chemicals
Alcohols Culture Media, Serum-Free Oligonucleotides, Antisense Receptors, Transforming Growth Factor beta Tgfb1 protein, rat Transforming Growth Factor beta Transforming Growth Factor beta1 RNA Collagen Protein Serine-Threonine Kinases Receptor, Transforming Growth Factor-beta Type II Ribonucleases Acetaldehyde
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Chen Anping
Department of Pathology, Louisiana State University Health Sciences Center in Shreveport, 1501 Kings Hwy., Shreveport, LA 71130, USA. achen@lsuhsc.edu
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/BJ20020949
Email
achen@lsuhsc.edu
Published
2002-12-15
Pages
683-93
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1223035
Subset
IM
External Links
PubMed source DOI: 10.1042/BJ20020949 PMC Full Text View journal details
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