Bezafibrate reduces the damage, activation and mechanical properties of lung fibroblast cells induced by hydrogen peroxide

Reghelin, Camille Kirinus; Bastos, Matheus Scherer; Basso, Bruno de Souza; Costa, Bruna Pasqualotto; Lima, Kelly Goulart; Sousa, Arieli Cruz de; Haute, Gabriela Viegas; Diz, Fernando Mendonça; Dias, Henrique Bregolin; Luft, Carolina; Rodrigues, Kétlin Fernanda; Garcia, Maria Cláudia Rosa; Matzenbacher, Lucas Strassburger; Adami, Bruno Silveira; Xavier, Léder Leal; Donadio, Márcio Vinı́cius Fagundes; Oliveira, Jarbas Rodrigues de; Melo, Denizar Alberto da Silva

doi:10.1007/s00210-023-02595-2

Naunyn-Schmiedeberg's Arch Pharmacol

2023

DOI: 10.1007/s00210-023-02595-2

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Bezafibrate reduces the damage, activation and mechanical properties of lung fibroblast cells induced by hydrogen peroxide

Camille Kirinus Reghelin

Matheus Scherer Bastos

Bruno de Souza Basso

et al.

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2024

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Role of transient receptor potential ankyrin 1 in idiopathic pulmonary fibrosis: modulation of M2 macrophage polarization

Yang,

Xiao,

Yang

et al. 2024

Cell. Mol. Life Sci.

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Idiopathic pulmonary fibrosis (IPF) poses significant challenges due to limited treatment options despite its complex pathogenesis involving cellular and molecular mechanisms. This study investigated the role of transient receptor potential ankyrin 1 (TRPA1) channels in regulating M2 macrophage polarization in IPF progression, potentially offering novel therapeutic targets. Using a bleomycin-induced pulmonary fibrosis model in C57BL/6J mice, we assessed the therapeutic potential of the TRPA1 inhibitor HC-030031. TRPA1 upregulation was observed in fibrotic lungs, correlating with worsened lung function and reduced survival. TRPA1 inhibition mitigated fibrosis severity, evidenced by decreased collagen deposition and restored lung tissue stiffness. Furthermore, TRPA1 blockade reversed aberrant M2 macrophage polarization induced by bleomycin, associated with reduced Smad2 phosphorylation in the TGF-β1-Smad2 pathway. In vitro studies with THP-1 cells treated with bleomycin and HC-030031 corroborated these findings, highlighting TRPA1's involvement in fibrotic modulation and macrophage polarization control. Overall, targeting TRPA1 channels presents promising therapeutic potential in managing pulmonary fibrosis by reducing pro-fibrotic marker expression, inhibiting M2 macrophage polarization, and diminishing collagen deposition. This study sheds light on a novel avenue for therapeutic intervention in IPF, addressing a critical need in the management of this challenging disease. Graphical abstract

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Role of transient receptor potential ankyrin 1 in idiopathic pulmonary fibrosis: modulation of M2 macrophage polarization

Yang,

Xiao,

Yang

et al. 2024

Cell. Mol. Life Sci.

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show abstract

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Bezafibrate reduces the damage, activation and mechanical properties of lung fibroblast cells induced by hydrogen peroxide

Cited by 1 publication

References 43 publications

Role of transient receptor potential ankyrin 1 in idiopathic pulmonary fibrosis: modulation of M2 macrophage polarization

Role of transient receptor potential ankyrin 1 in idiopathic pulmonary fibrosis: modulation of M2 macrophage polarization

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