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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.
Biochem J. 2002 Dec 15; 368(Pt 3):683-93.BJ

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.

Authors+Show Affiliations

Department of Pathology, Louisiana State University Health Sciences Center in Shreveport, 1501 Kings Hwy., Shreveport, LA 71130, USA. achen@lsuhsc.edu

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12223100

Citation

Chen, Anping. "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, pp. 683-93.
Chen A. 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. Biochem J. 2002;368(Pt 3):683-93.
Chen, A. (2002). 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, 368(Pt 3), 683-93.
Chen A. 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. Biochem J. 2002 Dec 15;368(Pt 3):683-93. PubMed PMID: 12223100.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. A1 - Chen,Anping, PY - 2002/09/11/accepted PY - 2002/09/09/revised PY - 2002/06/19/received PY - 2002/9/12/pubmed PY - 2003/2/11/medline PY - 2002/9/12/entrez SP - 683 EP - 93 JF - The Biochemical journal JO - Biochem J VL - 368 IS - Pt 3 N2 - 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. SN - 0264-6021 UR - https://www.unboundmedicine.com/medline/citation/12223100/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_ L2 - https://portlandpress.com/biochemj/article-lookup/doi/10.1042/BJ20020949 DB - PRIME DP - Unbound Medicine ER -