| Autor: |
Hsiao-Yen Ma, Jason A. Vander Heiden, Salil Uttarwar, Ying Xi, Elsa-Noah N'Diaye, Ryan LaCanna, Patrick Caplazi, Sarah Gierke, John Moffat, Paul J. Wolters, Ning Ding |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
The European respiratory journal. |
| ISSN: |
1399-3003 |
| Popis: |
BackgroundIdiopathic 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.MethodsWe performed transcriptomic and immunofluorescence analyses of primary human IPF tissues.ResultsWe 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 concentration 50–150 µM, maximal inhibition >90%, maximal concentration of PFD in patients ConclusionsOur results suggest MRTF signalling as a direct target for PFD and implicate that some of the anti-fibrotic effects of PFD may be due to MRTF inhibition in lung fibroblasts. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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