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Geiger, F.* ; Zeitlmayr, S.* ; Staab-Weijnitz, C.A. ; Rajan, S.* ; Breit, A.* ; Gudermann, T.* ; Dietrich, A.*

An inhibitory function of TRPA1 channels in TGF-β1-driven fibroblast to myofibroblast differentiation.

Am. J. Respir. Cell Mol. Biol. 68, 314-325 (2022)
Postprint DOI PMC
Open Access Green
Transient receptor potential ankyrin 1 (TRPA1) is a non-selective 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 transforming growth factor β1 (TGF-β1)-driven fibroblast to myofibroblast differentiation and the development of pulmonary fibrosis remains elusive. TRPA1 expression and function was analyzed in cultured primary HLFs, and mRNA levels were significantly reduced after adding TGF-β1. Expression of genes encoding fibrosis markers, e.g. alpha smooth muscle actin (ACTA2), plasminogen activator inhibitor 1 (SERPINE1), fibronectin (FN1) and type I collagen (COL1A1) was increased after siRNA-mediated down-regulation 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 enhanced apoptosis. Most interestingly, AITC-induced TRPA1 activation augmented ERK1/2 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Erk1/2 ; Smad2 ; Alpha Smooth Muscle Actin ; Plasminogen Activator Inhibitor 1 ; Type I Collagen; Idiopathic Pulmonary-fibrosis; Cells; Pathogenesis; Pathway
ISSN (print) / ISBN 1044-1549
e-ISSN 1535-4989
Zeitschrift American Journal of Respiratory Cell and Molecular Biology
Quellenangaben Band: 68, Heft: 3, Seiten: 314-325 Artikelnummer: , Supplement: ,
Verlag American Thoracic Society
Verlagsort 25 Broadway, 18 Fl, New York, Ny 10004 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Lung Health and Immunity (LHI)
Förderungen Deutsche Forschungsgemeinschaft
Deutsches Zentrum für Lungenforschung