{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:40:07Z","timestamp":1790505607991,"version":"4.1.0"},"reference-count":46,"publisher":"American Physiological Society","issue":"5","funder":[{"name":"US National Institute of Health","award":["R01HL095397"],"award-info":[{"award-number":["R01HL095397"]}]},{"name":"US National Institute of Health","award":["R01HL127349"],"award-info":[{"award-number":["R01HL127349"]}]},{"name":"American Lung Association Award","award":["RT 350419"],"award-info":[{"award-number":["RT 350419"]}]},{"name":"Marie Sklodowska\/Curie","award":["ERS\/EU-RESPIRE 2-8860-2015"],"award-info":[{"award-number":["ERS\/EU-RESPIRE 2-8860-2015"]}]},{"name":"Hellenic Thoracic Society","award":["Unrestricted Grant"],"award-info":[{"award-number":["Unrestricted Grant"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:p> Mitogen-activated protein kinase (MAPK) phosphatase 5 (MKP-5) is a member of the dual-specificity family of protein tyrosine phosphatases that negatively regulates p38 MAPK and the JNK. MKP-5-deficient mice exhibit improved muscle repair and reduced fibrosis in an animal model of muscular dystrophy. Here, we asked whether the effects of MKP-5 on muscle fibrosis extend to other tissues. Using a bleomycin-induced model of pulmonary fibrosis, we found that MKP-5-deficient mice were protected from the development of lung fibrosis, expressed reduced levels of hydroxyproline and fibrogenic genes, and displayed marked polarization towards an M1-macrophage phenotype. We showed that the profibrogenic effects of the transforming growth factor-\u03b21 (TGF-\u03b21) were inhibited in MKP-5-deficient lung fibroblasts. MKP-5-deficient fibroblasts exhibited enhanced p38 MAPK activity, impaired Smad3 phosphorylation, increased Smad7 levels, and decreased expression of fibrogenic genes. Myofibroblast differentiation was attenuated in MKP-5-deficient fibroblasts. Finally, we found that MKP-5 expression was increased in idiopathic pulmonary fibrosis (IPF)-derived lung fibroblasts but not in whole IPF lungs. These data suggest that MKP-5 plays an essential role in promoting lung fibrosis. Our results couple MKP-5 with the TGF-\u03b21 signaling machinery and imply that MKP-5 inhibition may serve as a therapeutic target for human lung fibrosis. <\/jats:p>","DOI":"10.1152\/ajplung.00264.2018","type":"journal-article","created":{"date-parts":[[2019,9,4]],"date-time":"2019-09-04T15:40:50Z","timestamp":1567611650000},"page":"L678-L689","source":"Crossref","is-referenced-by-count":34,"title":["Role of dual-specificity protein phosphatase DUSP10\/MKP-5 in pulmonary fibrosis"],"prefix":"10.1152","volume":"317","author":[{"given":"Nikos","family":"Xylourgidis","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kisuk","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, University of Texas, El Paso, 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