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An Inhibitory Function of TRPA1 Channels in TGF-β1-driven Fibroblast-to-Myofibroblast Differentiation.
- Source :
- American Journal of Respiratory Cell & Molecular Biology; Mar2023, Vol. 68 Issue 3, p314-325, 12p
- Publication Year :
- 2023
-
Abstract
- TRPA1 (transient receptor potential ankyrin 1) is a nonselective Ca2+-permeable cation channel, which was originally cloned from human lung fibroblasts (HLFs). TRPA1-mediated Ca2+ entry is evoked by exposure to several chemicals, including allyl isothiocyanate (AITC), and a protective effect of TRPA1 activation in the development of cardiac fibrosis has been proposed. Yet the function of TRPA1 in TGF-β1 (transforming growth factor-β1)-driven fibroblast-to-myofibroblast differentiation and the development of pulmonary fibrosis remains elusive. TRPA1 expression and function were analyzed in cultured primary HLFs, and mRNA concentrations were significantly reduced after adding TGF-β1. Expression of genes encoding fibrosis markers (e.g., ACTA2, SERPINE1 [plasminogen activator inhibitor 1], FN1 [fibronectin], COL1A1 [type I collagen]) was increased after siRNA-mediated downregulation of TRPA1 mRNA in HLFs. Moreover, AITC-induced Ca2+ entry in HLFs was decreased after TGF-β1 treatment and by application of TRPA1 siRNAs, while AITC treatment alone did not reduce cell viability or enhance apoptosis. Most interestingly, AITC-induced TRPA1 activation augmented ERK1/2 (extracellular signal-regulated kinase 1/2) and SMAD2 linker phosphorylation, which might inhibit TGF-β-receptor signaling. Our results suggest an inhibitory function of TRPA1 channels in TGF-β1-driven fibroblast-to-myofibroblast differentiation. Therefore, activation of TRPA1 channels might be protective during the development of pulmonary fibrosis in patients. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10441549
- Volume :
- 68
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- American Journal of Respiratory Cell & Molecular Biology
- Publication Type :
- Academic Journal
- Accession number :
- 162221209
- Full Text :
- https://doi.org/10.1165/rcmb.2022-0159OC