التفاصيل البيبلوغرافية
| العنوان: |
MAPK phosphatase 1 inhibition of p38a within lung myofibroblasts is essential for spontaneous fibrosis resolution. |
| المؤلفون: |
Fortier, Sean M.1, Walker, Natalie M.1, Penke, Loka R.1, Baas, Jared D.1, Qinxue Shen1,2, Speth, Jennifer M.1, Huang, Steven K.1, Zemans, Rachel L.1, Bennett, Anton M.3, Peters-Golden, Marc1 petersm@umich.edu |
| المصدر: |
Journal of Clinical Investigation. 5/15/2024, Vol. 134 Issue 10, p1-17. 17p. |
| مصطلحات موضوعية: |
*MITOGEN-activated protein kinase phosphatases, *MYOFIBROBLASTS, *FIBROSIS, *LUNGS, *PULMONARY fibrosis, *LIPOXINS |
| مستخلص: |
Fibrosis following tissue injury is distinguished from normal repair by the accumulation of pathogenic and apoptosisresistant myofibroblasts (MFs), which arise primarily by differentiation from resident fibroblasts. Endogenous molecular brakes that promote MF dedifferentiation and clearance during spontaneous resolution of experimental lung fibrosis may provide insights that could inform and improve the treatment of progressive pulmonary fibrosis in patients. MAPK phosphatase 1 (MKP1) influences the cellular phenotype and fate through precise and timely regulation of MAPK activity within various cell types and tissues, yet its role in lung fibroblasts and pulmonary fibrosis has not been explored. Using gain- and loss-of-function studies, we found that MKP1 promoted lung MF dedifferentiation and restored the sensitivity of these cells to apoptosis -- effects determined to be mainly dependent on MKP1's dephosphorylation of p38α MAPK (p38α). Fibroblast-specific deletion of MKP1 following peak bleomycin-induced lung fibrosis largely abrogated its subsequent spontaneous resolution. Such resolution was restored by treating these transgenic mice with the p38α inhibitor VX-702. We conclude that MKP1 is a critical antifibrotic brake whose inhibition of pathogenic p38α in lung fibroblasts is necessary for fibrosis resolution following lung injury. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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