ArticleRespiratory research2021
AITC inhibits fibroblast-myofibroblast transition via TRPA1-independent MAPK and NRF2/HO-1 pathways and reverses corticosteroids insensitivity in human lung fibroblasts.
Article in Respiratory research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 22 citations in OpenAlex.
- Construction of a dual-compartment hydrogel by protein-based triblock copolymer for theMaterials today. Bio · 2026Article
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- Health Benefits, Applications, and Analytical Methods of Freshly Produced Allyl Isothiocyanate.Foods (Basel, Switzerland) · 2025Review
- Modulating TRPV1 and TRPA1 channels: a viable strategy for treating asthma using Chinese herbal medicines.Frontiers in pharmacology · 2025Review
- HMGB1 derived from lung epithelial cells after cobalt nanoparticle exposure promotes the activation of lung fibroblasts.Nanotoxicology · 2024Article
- Dual role of transient receptor potential ankyrin 1 in respiratory and gastrointestinal physiology: From molecular mechanisms to therapeutic targets.Frontiers in physiology · 2024Review
- The inhibitory effect of quercetin-3-glucuronide on pulmonary injury in vitro and in vivo.Journal of food and drug analysis · 2023Article
- Activation of TRPA1 in Bladder Suburothelial Myofibroblasts Counteracts TGF-β1-Induced Fibrotic Changes.International journal of molecular sciences · 2023Article
- Review
- Investigation of the Role of the TRPA1 Ion Channel in Conveying the Effect of Dimethyl Trisulfide on Vascular and Histological Changes in Serum-Transfer Arthritis.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Function and therapeutic potential of transient receptor potential ankyrin 1 in fibrosis.Frontiers in pharmacology · 2022Review
- Role of Nrf2 in Disease: Novel Molecular Mechanisms and Therapeutic Approaches - Pulmonary Disease/Asthma.Frontiers in physiology · 2021Review
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14 authors at 1 institution in 1 country.
Funding
Abstract
backgroundLittle is known on the role of transient receptor potential ankyrin 1 (TRPA1) in fibroblast-myofibroblast transition (FMT) that can lead to airway remodeling which is a major problem for severe asthma and fibrosis. Thus, this study investigated the effect of TRPA1 modulators on transforming growth factor beta 1(TGF-β1) -treated lung fibroblasts.
methodsMRC-5 cells were preincubated with TGF-β1 for 24 h. TRPA1 agonist or antagonist were added and further incubated for 24 h. The changes in TRPA1 and alpha-smooth muscle actin (α-SMA) expressions by stimuli were evaluated using qRT-PCR, western blot and immunohistochemical analyses. Statistical significance was determined by using one- or two-way ANOVA, followed by Bonferroni's post hoc analysis for comparison of multiple groups and paired 2-tailed Student's t-test between 2 groups.
resultsMRC-5 cells treated by TGF-β1 significantly upregulated α-SMA mRNA expressions (P < 0.01), but downregulated TRPA1 gene expression (P < 0.001). Post-treatment of TRPA1 activator, allyl isothiocyanate (AITC), after TGF-β1 significantly downregulated the α-SMA gene induction (P < 0.01 at 24 h), protein expression (P < 0.05) and immunoreactivity with stress fibers (P < 0.05). On the other hand, TRPA1 antagonist HC-030031 did not prevent this effect, and instead tended to facilitate the suppressive effect of AITC when co-stimulated. AITC significantly increased phosphorylated- extracellular signal-regulated kinase (ERK) 1/2 and heme oxygenase (HO)-1 protein expressions (P < 0.05) in TGF-β1-treated cells. Combined inhibition with ERK1/2 mitogen-activated protein kinase (MAPK) and nuclear factor erythroid 2-related factor (NRF2) almost completely reversed AITC-induced α-SMA suppression (P < 0.05). Dexamethasone was not able to inhibit the upregulated α-SMA induction by TGF-β1. However, AITC improved dexamethasone-insensitive myodifferentiation in the presence of the corticosteroid (P < 0.01).
conclusionWe found that AITC exerts protective effect on TGF-β1-induced α-SMA induction by activating ERK1/2 MAPK and NRF2/HO-1 pathways in lung fibroblasts. It also overcomes corticosteroids insensitivity in TGF-β1-induced α-SMA induction. TRPA1 antagonist modulates the suppressive effect, but not prevent it. AITC and TRPA1 antagonist may be therapeutic agents in treating chronic respiratory diseases.
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