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AITC inhibits fibroblast-myofibroblast transition via TRPA1-independent MAPK and NRF2/HO-1 pathways and reverses corticosteroids insensitivity in human lung fibroblasts.


ABSTRACT:

Background

Little 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-?1) -treated lung fibroblasts.

Methods

MRC-5 cells were preincubated with TGF-?1 for 24 h. TRPA1 agonist or antagonist were added and further incubated for 24 h. The changes in TRPA1 and alpha-smooth muscle actin (?-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.

Results

MRC-5 cells treated by TGF-?1 significantly upregulated ?-SMA mRNA expressions (P?ConclusionWe found that AITC exerts protective effect on TGF-?1-induced ?-SMA induction by activating ERK1/2 MAPK and NRF2/HO-1 pathways in lung fibroblasts. It also overcomes corticosteroids insensitivity in TGF-?1-induced ?-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.

SUBMITTER: Yap JMG 

PROVIDER: S-EPMC7881560 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

AITC inhibits fibroblast-myofibroblast transition via TRPA1-independent MAPK and NRF2/HO-1 pathways and reverses corticosteroids insensitivity in human lung fibroblasts.

Yap Jennifer Maries Go JMG   Ueda Takashi T   Kanemitsu Yoshihiro Y   Takeda Norihisa N   Fukumitsu Kensuke K   Fukuda Satoshi S   Uemura Takehiro T   Tajiri Tomoko T   Ohkubo Hirotsugu H   Maeno Ken K   Ito Yutaka Y   Oguri Testsuya T   Ugawa Shinya S   Niimi Akio A  

Respiratory research 20210212 1


<h4>Background</h4>Little 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.<h4>Methods</h4>MRC-5 cells were preincubated with TGF-β1 for 24 h. TRPA1 agonist or antagonist were added and further incubated for 2  ...[more]

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