Dataset Information

Pirfenidone attenuates lung fibrotic fibroblast responses to transforming growth factor-β1.

ABSTRACT:

Background

Pirfenidone, an antifibrotic agent used for the treatment of idiopathic pulmonary fibrosis (IPF), functions by inhibiting myofibroblast differentiation, which is involved in transforming growth factor (TGF)-β1-induced IPF pathogenesis. However, unlike normal lung fibroblasts, the relationship between pirfenidone responses of TGF-β1-induced human fibrotic lung fibroblasts and lung fibrosis has not been elucidated.

Methods

The effects of pirfenidone were evaluated in lung fibroblasts isolated from fibrotic human lung tissues after TGF-β1 exposure. The ability of two new pharmacological targets of pirfenidone, collagen triple helix repeat containing protein 1(CTHRC1) and four-and-a-half LIM domain protein 2 (FHL2), to mediate contraction of collagen gels and migration toward fibronectin were assessed in vitro.

Results

Compared to control lung fibroblasts, pirfenidone significantly restored TGF-β1-stimulated fibroblast-mediated collagen gel contraction, migration, and CTHRC1 release in lung fibrotic fibroblasts. Furthermore, pirfenidone attenuated TGF-β1- and CTHRC1-induced fibroblast activity, upregulation of bone morphogenic protein-4(BMP-4)/Gremlin1, and downregulation of α-smooth muscle actin, fibronectin, and FHL2, similar to that observed post-CTHRC1 inhibition. In contrast, FHL2 inhibition suppressed migration and fibronectin expression, but did not downregulate CTHRC1.

Conclusions

Overall, pirfenidone suppressed fibrotic fibroblast-mediated fibrotic processes via inverse regulation of CTHRC1-induced lung fibroblast activity. Thus, CTHRC1 can be used for predicting pirfenidone response and developing new therapeutic targets for lung fibrosis.

SUBMITTER: Jin J

PROVIDER: S-EPMC6558902 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

Pirfenidone attenuates lung fibrotic fibroblast responses to transforming growth factor-β1.

Jin Jin J Togo Shinsaku S Kadoya Kotaro K Tulafu Miniwan M Namba Yukiko Y Iwai Moe M Watanabe Junko J Nagahama Kumi K Okabe Takahiro T Hidayat Moulid M Kodama Yuzo Y Kitamura Hideya H Ogura Takashi T Kitamura Norikazu N Ikeo Kazuho K Sasaki Shinichi S Tominaga Shigeru S Takahashi Kazuhisa K

Respiratory research 20190611 1

<h4>Background</h4>Pirfenidone, an antifibrotic agent used for the treatment of idiopathic pulmonary fibrosis (IPF), functions by inhibiting myofibroblast differentiation, which is involved in transforming growth factor (TGF)-β1-induced IPF pathogenesis. However, unlike normal lung fibroblasts, the relationship between pirfenidone responses of TGF-β1-induced human fibrotic lung fibroblasts and lung fibrosis has not been elucidated.<h4>Methods</h4>The effects of pirfenidone were evaluated in lung ...[more]

PMID: 31185973

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Dataset Information

Pirfenidone attenuates lung fibrotic fibroblast responses to transforming growth factor-β1.

Background

Methods

Results

Conclusions

Publications

Pirfenidone attenuates lung fibrotic fibroblast responses to transforming growth factor-β1.

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