{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T19:16:07Z","timestamp":1791832567648,"version":"4.3.4"},"reference-count":53,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T00:00:00Z","timestamp":1583971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2014\/14\/E\/NZ5\/00175"],"award-info":[{"award-number":["2014\/14\/E\/NZ5\/00175"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Progressive cardiac fibrosis is a common cause of heart failure. Rho-associated, coiled-coil-containing protein kinases (ROCKs) have been shown to enhance fibrotic processes in the heart and in other organs. In this study, using wild-type, Rock1+\/\u2212 and Rock2+\/\u2212 haploinsufficient mice and mouse model of experimental autoimmune myocarditis (EAM) we addressed the role of ROCK1 and ROCK2 in development of myocarditis and postinflammatory fibrosis. We found that myocarditis severity was comparable in wild-type, Rock1+\/\u2212 and Rock2+\/\u2212 mice at day 21 of EAM. During the acute stage of the disease, hearts of Rock1+\/\u2212 mice showed unaffected numbers of CD11b+CD36+ macrophages, CD11b+CD36\u2013Ly6GhiLy6chi neutrophils, CD11b+CD36\u2013Ly6G\u2013Ly6chi inflammatory monocytes, CD11b+CD36\u2013Ly6G\u2013Ly6c\u2013 monocytes, CD11b+SiglecF+ eosinophils, CD11b+CD11c+ inflammatory dendritic cells and type I collagen-producing fibroblasts. Isolated Rock1+\/\u2212 cardiac fibroblasts treated with transforming growth factor-beta (TGF-\u03b2) showed attenuated Smad2 and extracellular signal-regulated kinase (Erk) phosphorylations that were associated with impaired upregulation of smooth muscle actin alpha (\u03b1SMA) protein. In contrast to cardiac fibroblasts, expanded Rock1+\/\u2212 heart inflammatory myeloid cells showed unaffected Smad2 activation but enhanced Erk phosphorylation following TGF-\u03b2 treatment. Rock1+\/\u2212 inflammatory cells responded to TGF-\u03b2 by a reduced transcriptional profibrotic response and failed to upregulate \u03b1SMA and fibronectin at the protein levels. Unexpectedly, in the EAM model wild-type, Rock1+\/\u2212 and Rock2+\/\u2212 mice developed a similar extent of cardiac fibrosis at day 40. In addition, hearts of the wild-type and Rock1+\/\u2212 mice showed comparable levels of cardiac vimentin, periostin and \u03b1SMA. In conclusion, despite the fact that ROCK1 regulates TGF-\u03b2-dependent profibrotic response, neither ROCK1 nor ROCK2 is critically involved in the development of postinflammatory fibrosis in the EAM model.<\/jats:p>","DOI":"10.3390\/cells9030700","type":"journal-article","created":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T08:58:59Z","timestamp":1584089939000},"page":"700","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Haploinsufficient Rock1+\/\u2212 and Rock2+\/\u2212 Mice Are Not Protected from Cardiac Inflammation and Postinflammatory Fibrosis in Experimental Autoimmune Myocarditis"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4707-9126","authenticated-orcid":false,"given":"Karolina","family":"Tkacz","sequence":"first","affiliation":[{"name":"Department of Clinical Immunology, Jagiellonian University Medical College, 30-663 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"Rolski","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Jagiellonian University Medical College, 30-663 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4402-1738","authenticated-orcid":false,"given":"Marcin","family":"Czepiel","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Jagiellonian University Medical College, 30-663 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edyta","family":"Dzia\u0142o","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Jagiellonian University Medical College, 30-663 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3904-5412","authenticated-orcid":false,"given":"Maciej","family":"Siedlar","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Jagiellonian University Medical College, 30-663 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urs","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Cardioimmunology, Center for Molecular Cardiology, University of Zurich, 8952 Schlieren, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Kania","sequence":"additional","affiliation":[{"name":"Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, 8952 Schlieren, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2521-3232","authenticated-orcid":false,"given":"Przemys\u0142aw","family":"B\u0142yszczuk","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Jagiellonian University Medical College, 30-663 Cracow, Poland"},{"name":"Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, 8952 Schlieren, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.matbio.2018.01.013","article-title":"Extracellular matrix remodeling and cardiac fibrosis","volume":"68\u201369","author":"Li","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s00018-013-1349-6","article-title":"The pathogenesis of cardiac fibrosis","volume":"71","author":"Kong","year":"2014","journal-title":"Cell. 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