{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T22:24:37Z","timestamp":1777933477640,"version":"3.51.4"},"reference-count":53,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T00:00:00Z","timestamp":1677542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Academy of Finland"},{"name":"Competitive research funding (VTR funding) by Tampere University Hospital"},{"name":"Pirkanmaa Regional Fund of the Finnish Cultural Foundation"},{"name":"Tampere Tuberculosis Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Scleroderma is a chronic fibrotic disease, where proinflammatory and profibrotic events precede collagen accumulation. MKP-1 [mitogen-activated protein kinase (MAPK) phosphatase-1] downregulates inflammatory MAPK pathways suppressing inflammation. MKP-1 also supports Th1 polarization, which could shift Th1\/Th2 balance away from profibrotic Th2 profile prevalent in scleroderma. In the present study, we investigated the potential protective role of MKP-1 in scleroderma. We utilized bleomycin-induced dermal fibrosis model as a well-characterized experimental model of scleroderma. Dermal fibrosis and collagen deposition as well as the expression of inflammatory and profibrotic mediators were analyzed in the skin samples. Bleomycin-induced dermal thickness and lipodystrophy were increased in MKP-1-deficient mice. MKP-1 deficiency enhanced collagen accumulation and increased expression of collagens, 1A1 and 3A1, in the dermis. Bleomycin-treated skin from MKP-1-deficient mice also showed enhanced expression of inflammatory and profibrotic factors IL-6, TGF-\u03b21, fibronectin-1 and YKL-40, and chemokines MCP-1, MIP-1\u03b1 and MIP-2, as compared to wild-type mice. The results show, for the first time, that MKP-1 protects from bleomycin-induced dermal fibrosis, suggesting that MKP-1 favorably modifies inflammation and fibrotic processes that drive the pathogenesis of scleroderma. Compounds enhancing the expression or activity of MKP-1 could thus prevent fibrotic processes in scleroderma and possess potential as a novel immunomodulative drug.<\/jats:p>","DOI":"10.3390\/ijms24054668","type":"journal-article","created":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T04:28:41Z","timestamp":1677558521000},"page":"4668","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["MKP-1 Deficiency Exacerbates Skin Fibrosis in a Mouse Model of Scleroderma"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1150-2933","authenticated-orcid":false,"given":"Morena","family":"Scotece","sequence":"first","affiliation":[{"name":"The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, 33014 Tampere, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mari","family":"H\u00e4m\u00e4l\u00e4inen","sequence":"additional","affiliation":[{"name":"The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, 33014 Tampere, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiina","family":"Lepp\u00e4nen","sequence":"additional","affiliation":[{"name":"The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, 33014 Tampere, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0017-1291","authenticated-orcid":false,"given":"Katriina","family":"Vuolteenaho","sequence":"additional","affiliation":[{"name":"The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, 33014 Tampere, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8577-0316","authenticated-orcid":false,"given":"Eeva","family":"Moilanen","sequence":"additional","affiliation":[{"name":"The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, 33014 Tampere, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1016\/S0140-6736(17)30933-9","article-title":"Systemic Sclerosis","volume":"390","author":"Denton","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/s41584-019-0184-z","article-title":"Emerging Targets of Disease-Modifying Therapy for Systemic Sclerosis","volume":"15","author":"Volkmann","year":"2019","journal-title":"Nat. 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