ArticleAlcoholism, clinical and experimental research2017
MiR-21-Mediated Suppression of Smad7 Induces TGFβ1 and Can Be Inhibited by Activation of Nrf2 in Alcohol-Treated Lung Fibroblasts.
Article in Alcoholism, clinical and experimental research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 19 citations in OpenAlex.
- Nrf2 and STAT3 Pathways in Protecting Against Methylmercury-Induced Oxidative Stress in Hypothalamic Neuronal GT1-7 Cells.Neurochemical research · 2026Article
- Circular RNA RORβ regulates TGFβR1 in alcohol-induced fibroblast-to-myofibroblast differentiation.Scientific reports · 2025Article
- Ethanol-induced Nrf2 suppression in the lung is mediated by AP-1-driven expression of miR-144.Alcohol, clinical & experimental research · 2025Article
- Ethanol-exposed lung fibroblasts cause airway epithelial barrier dysfunction.Alcohol, clinical & experimental research · 2023Article
- Alterations in plasma miR-21, miR-590, miR-192 and miR-215 in idiopathic pulmonary fibrosis and their clinical importance.Molecular biology reports · 2022Article
- Astaxanthin attenuates hepatic steatosis in high-fat diet-fed rats by suppressing microRNA-21 via transactivation of nuclear factor erythroid 2-related factor 2.Journal of physiology and biochemistry · 2022Article
- MicroRNA-21 inhibition attenuates airway inflammation and remodelling by modulating the transforming growth factor β-Smad7 pathway.The Korean journal of internal medicine · 2021Article
- Transforming Growth Factor-β1 Promotes M1 Alveolar Macrophage Polarization in Acute Lung Injury by Up-Regulating DNMT1 to Mediate the microRNA-124/PELI1/IRF5 Axis.Frontiers in cellular and infection microbiology · 2021Article
- Alcohol induces TGFβ1 via downregulation of miR-1946a in murine lung fibroblast.Scientific reports · 2020Article
- Folate pathways mediating the effects of ethanol in tumorigenesis.Chemico-biological interactions · 2020Review
- Review
- MiR-144 mediates Nrf2 inhibition and alveolar epithelial dysfunction in HIV-1 transgenic rats.American journal of physiology. Cell physiology · 2019Article
- MicroRNA-21-5p promotes proliferation of gastric cancer cells through targeting SMAD7.OncoTargets and therapy · 2018Article
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Authors and funding
5 authors at 2 institutions in 1 country.
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Abstract
backgroundWe previously demonstrated that chronic alcohol ingestion augments TGFβ1 expression in the lung fibroblast and increases the risk of fibroproliferative disrepair in a mouse model of acute lung injury. The effect of alcohol on TGFβ1 is mitigated by treatment with sulforaphane (SFP), which can activate nuclear factor (erythroid-derived 2)-like 2 (Nrf2). However, the mechanisms by which alcohol amplifies, or SFP attenuates, TGFβ1 expression in the fibroblast are not known. MicroRNA (miR)-21 has been shown to inhibit Smad7, a TGFβ1 signaling inhibitor. In this study, we hypothesized that alcohol augments TGFβ1 expression through up-regulation of miR-21, which subsequently inhibits Smad7.
methodsPrimary mouse lung fibroblasts were cultured ± alcohol ± SFP and assessed for gene expression of miR-21, and gene and/or protein expression of Nrf2, Nrf2-regulated antioxidant enzymes, Smad7, STAT3, and TGFβ1. NIH 3T3 fibroblasts were transfected with a miR-21 inhibitor and cultured ± alcohol. α-SMA, Smad7, and TGFβ1 protein expression were then assessed. In parallel, NIH 3T3 lung fibroblasts were transfected with Nrf2 silencing RNA (siRNA) and cultured ± alcohol ± SFP. Gene expression of miR-21, Nrf2, Smad7, and TGFβ1 was assessed.
resultsMiR-21 gene expression was increased by 12-fold at 48 hours, and Smad7 gene expression and protein expression were reduced by ~30% in alcohol-treated fibroblasts. In parallel, inhibition of miR-21 attenuated alcohol-mediated decrease in Smad7 and increase in TGFβ1 and α-SMA protein expression. Treatment with SFP mitigated the effect of alcohol on miR-21, Smad7 and total and phosphorylated STAT3, and restored Nrf2-regulated antioxidant gene expression. Silencing of Nrf2 prevented the effect of SFP on miR-21, Smad7, and TGFβ1 gene expression in alcohol-treated NIH 3T3 fibroblasts.
conclusionsAlcohol treatment increases TGFβ1 in fibroblasts, at least in part, through augmentation of miR-21, which then inhibits Smad7 expression. These effects can be attenuated by activation of Nrf2 with SFP.
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