ArticleWorld journal of gastroenterology2016
New role and molecular mechanism of Gadd45a in hepatic fibrosis.
Article in World journal of gastroenterology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
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Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- Research trends of mitochondrial dysfunction in hepatic fibrosis: a bibliometric analysis.Frontiers in physiology · 2026Pooled it
- Contradictory Role of Gadd45β in Liver Diseases.Journal of cellular and molecular medicine · 2024Pooled it
- Longevity-driven hepatic transcriptional programs mediate resilience to diet-induced liver injury in Ames dwarf mice.GeroScience · 2026Article
- The PERK-GADD45A axis is a key driver of hepatic stellate cell activation.Hepatology communications · 2026Article
- GADD45A suppression contributes to cardiac remodeling by promoting inflammation, fibrosis and hypertrophy.Cellular and molecular life sciences : CMLS · 2025Article
- Stress and Liver Fibrogenesis: Understanding the Role and Regulation of Stress Response Pathways in Hepatic Stellate Cells.The American journal of pathology · 2023Review
- Polymorphisms within DIO2 and GADD45A genes increase the risk of liver disease progression in chronic hepatitis b carriers.Scientific reports · 2023Article
- Identification of Drug-Induced Liver Injury Biomarkers from Multiple Microarrays Based on Machine Learning and Bioinformatics Analysis.International journal of molecular sciences · 2022Article
- Resistin deletion protects against heart failure injury by targeting DNA damage response.Cardiovascular research · 2022Article
- Deriving time-concordant event cascades from gene expression data: A case study for Drug-Induced Liver Injury (DILI).PLoS computational biology · 2022Article
- Gadd45 in Senescence.Advances in experimental medicine and biology · 2022Article
- Integrative Analysis of Nanopore and Illumina Sequencing Reveals Alternative Splicing Complexity in Pig Longissimus Dorsi Muscle.Frontiers in genetics · 2022Article
- Gadd45 in the Liver: Signal Transduction and Transcriptional Mechanisms.Advances in experimental medicine and biology · 2022Article
- Histone H3K27 methyltransferase EZH2 and demethylase JMJD3 regulate hepatic stellate cells activation and liver fibrosis.Theranostics · 2021Article
- Comparative analysis of the expression profiles of genes related to the Gadd45α signaling pathway in four kinds of liver diseases.Histology and histopathology · 2020Article
- Unfolded protein response is an early, non-critical event during hepatic stellate cell activation.Cell death & disease · 2019Article
- GADD45α alleviates acetaminophen-induced hepatotoxicity by promoting AMPK activation.Cellular and molecular life sciences : CMLS · 2019Article
- Growth arrest and DNA damage-inducible 45α protects against nonalcoholic steatohepatitis induced by methionine- and choline-deficient diet.Biochimica et biophysica acta. Molecular basis of disease · 2017Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo investigate the role of Gadd45a in hepatic fibrosis and the transforming growth factor (TGF)-β/Smad signaling pathway.
methodsWild-type male BALB/c mice were treated with CCl4 to induce a model of chronic liver injury. Hepatic stellate cells (HSCs) were isolated from the liver of BALB/c mice and were treated with small interfering RNAs (siRNAs) targeting Gadd45a or the pcDNA3.1-Gadd45a recombinant plasmid. Cellular α-smooth muscle actin (α-SMA), β-actin, type I collagen, phospho-Smad2, phospho-Smad3, Smad2, Smad3, and Smad4 were detected by Western blots. The mRNA levels of α-SMA, β-actin, and type I collagen were determined by quantitative real-time (qRT)-PCR analyses. Reactive oxygen species production was monitored by flow cytometry using 2,7-dichlorodihydrofluorescein diacetate. Gadd45a, Gadd45b, anti-Gadd45g, type I collagen, and SMA local expression in liver tissue were measured by histologic and immunohistochemical analyses.
resultsSignificant downregulation of Gadd45a, but not Gadd45b or Gadd45g, accompanied by activation of the TGF-β/Smad signaling pathways was detected in fibrotic liver tissues of mice and isolated HSCs with chronic liver injury induced by CCl4 treatment. Overexpression of Gadd45a reduced the expression of extracellular matrix proteins and α-SMA in HSCs, whereas transient knockdown of Gadd45a with siRNA reversed this process. Gadd45a inhibited the activity of a plasminogen activator inhibitor-1 promoter construct and (CAGA)9 MLP-Luc, an artificial Smad3/4-specific reporter, as well as reduced the phosphorylation and nuclear translocation of Smad3. Gadd45a showed protective effects by scavenging reactive oxygen species and upregulating antioxidant enzymes.
conclusionGadd45a may counteract hepatic fibrosis by regulating the activation of HSCs via the inhibition of TGF-β/Smad signaling.
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