Inhibition of MRTF activation as a clinically achievable anti-fibrotic mechanism for pirfenidone.

ABSTRACT:

Background

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease characterised by aberrant fibroblast/myofibroblast accumulation and excessive collagen matrix deposition in the alveolar areas of lungs. As the first approved IPF medication, pirfenidone (PFD) significantly decelerates lung function decline while its underlying anti-fibrotic mechanism remains elusive.

Methods

We performed transcriptomic and immunofluorescence analyses of primary human IPF tissues.

Results

We showed that myocardin-related transcription factor (MRTF) signalling is activated in myofibroblasts accumulated in IPF lungs. Furthermore, we showed that PFD inhibits MRTF activation in primary human lung fibroblasts at clinically achievable concentrations (half-maximal inhibitory con

SUBMITTER: Ma HY 

PROVIDER: S-EPMC10133585 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature