ArticleThe American journal of pathology2014
Mechanisms of action of acetaldehyde in the up-regulation of the human α2(I) collagen gene in hepatic stellate cells: key roles of Ski, SMAD3, SMAD4, and SMAD7.
Article in The American journal of pathology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Linking fatty liver diseases to hepatocellular carcinoma by hepatic stellate cells.Journal of the National Cancer Center · 2024Review
- Unaltered hepatic wound healing response in male rats with ancestral liver injury.Nature communications · 2023Article
- A Meta-Analysis of Preclinical Studies to Investigate the Effect ofAntioxidants (Basel, Switzerland) · 2023Review
- Mycoviruses in Fungi: Carcinogenesis of Fungal Agents May Not Always Be Mycotoxin Related.Journal of fungi (Basel, Switzerland) · 2023Article
- Overexpressed ski efficiently promotes neurorestoration, increases neuronal regeneration, and reduces astrogliosis after traumatic brain injury.Gene therapy · 2023Article
- A review on association of fungi with the development and progression of carcinogenesis in the human body.Current research in microbial sciences · 2022Review
- cAMP Signaling in Pathobiology of Alcohol Associated Liver Disease.Biomolecules · 2020Review
- Aldehyde Dehydrogenase, Liver Disease and Cancer.International journal of biological sciences · 2020Review
- Transcriptomic Profiling of Obesity-Related Nonalcoholic Steatohepatitis Reveals a Core Set of Fibrosis-Specific Genes.Journal of the Endocrine Society · 2018Article
- SREBP1c mediates the effect of acetaldehyde on Cidea expression in Alcoholic fatty liver Mice.Scientific reports · 2018Article
- Alpha Mangostin Inhibits the Proliferation and Activation of Acetaldehyde Induced Hepatic Stellate Cells through TGF-Journal of toxicology · 2018Article
- Intestinal flora imbalance promotes alcohol-induced liver fibrosis by the TGFβ/smad signaling pathway in mice.Oncology letters · 2017Article
- [Effect of interleukin-22 on proliferation and activation of hepatic stellate cells induced by acetaldehyde and related mechanism].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2017Article
- Evaluation of urinary bladder fibrogenesis in a mouse model of long-term ketamine injection.Molecular medicine reports · 2016Article
- Microarray Study of Pathway Analysis Expression Profile Associated with MicroRNA-29a with Regard to Murine Cholestatic Liver Injuries.International journal of molecular sciences · 2016Article
- Adipose tissue-liver axis in alcoholic liver disease.World journal of gastrointestinal pathophysiology · 2016Article
- Metabolic derivatives of alcohol and the molecular culprits of fibro-hepatocarcinogenesis: Allies or enemies?World journal of gastroenterology · 2016Review
- New Approaches for Studying Alcoholic Liver Disease.Current pathobiology reports · 2014Article
- Ethanol and High Cholesterol Diet Causes Severe Steatohepatitis and Early Liver Fibrosis in Mice.PloS oneArticle
- Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease.Signal transduction and targeted therapyArticle
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Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
Abstract
Alcohol-induced liver fibrosis and eventually cirrhosis is a leading cause of death. Acetaldehyde, the first metabolite of ethanol, up-regulates expression of the human α2(I) collagen gene (COL1A2). Early acetaldehyde-mediated effects involve phosphorylation and nuclear translocation of SMAD3/4-containing complexes that bind to COL1A2 promoter to induce fibrogenesis. We used human and mouse hepatic stellate cells to elucidate the mechanisms whereby acetaldehyde up-regulates COL1A2 by modulating the role of Ski and the expression of SMADs 3, 4, and 7. Acetaldehyde induced up-regulation of COL1A2 by 3.5-fold, with concomitant increases in the mRNA (threefold) and protein (4.2- and 3.5-fold) levels of SMAD3 and SMAD4, respectively. It also caused a 60% decrease in SMAD7 expression. Ski, a member of the Ski/Sno oncogene family, is colocalized in the nucleus with SMAD4. Acetaldehyde induces translocation of Ski and SMAD4 to the cytoplasm, where Ski undergoes proteasomal degradation, as confirmed by the ability of the proteasomal inhibitor lactacystin to blunt up-regulation of acetaldehyde-dependent COL1A2, but not of the nonspecific fibronectin gene (FN1). We conclude that acetaldehyde up-regulates COL1A2 by enhancing expression of the transactivators SMAD3 and SMAD4 while inhibiting the repressor SMAD7, along with promoting Ski translocation from the nucleus to cytoplasm. We speculate that drugs that prevent proteasomal degradation of repressors targeting COL1A2 may have antifibrogenic properties.
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