{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T11:24:28Z","timestamp":1785237868747,"version":"3.55.0"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T00:00:00Z","timestamp":1543363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003092","name":"Diabetes Fonds","doi-asserted-by":"publisher","award":["2012.00.1471"],"award-info":[{"award-number":["2012.00.1471"]}],"id":[{"id":"10.13039\/501100003092","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>End\u2010stage renal disease, the final stage of all chronic kidney disorders, is associated with renal fibrosis and inevitably leads to renal failure and death. Transition of tubular epithelial cells (TECs) into mesenchymal fibroblasts constitutes a proposed mechanism underlying the progression of renal fibrosis and here we assessed whether protease\u2010activated receptor (PAR)\u20101, which recently emerged as an inducer of epithelial\u2010to\u2010mesenchymal transition (EMT), aggravates renal fibrosis. We show that PAR\u20101 activation on TECs reduces the expression of epithelial markers and simultaneously induces mesenchymal marker expression reminiscent of EMT. We next show that kidney damage was reduced in PAR\u20101\u2010deficient mice during unilateral ureter obstruction (UUO) and that PAR\u20101\u2010deficient mice develop a diminished fibrotic response. Importantly, however, we did hardly observe any signs of mesenchymal transition in both wild\u2010type and PAR\u20101\u2010deficient mice suggesting that diminished fibrosis in PAR\u20101\u2010deficient mice is not due to reduced EMT. Instead, the accumulation of macrophages and fibroblasts was significantly reduced in PAR\u20101\u2010deficient animals which were accompanied by diminished production of MCP\u20101 and TGF\u2010\u03b2. Overall, we thus show that PAR\u20101 drives EMT of TECs in vitro and aggravates UUO\u2010induced renal fibrosis although this is likely due to PAR\u20101\u2010dependent pro\u2010fibrotic cytokine production rather than EMT.<\/jats:p>","DOI":"10.1111\/jcmm.14028","type":"journal-article","created":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T12:59:13Z","timestamp":1543409953000},"page":"1268-1279","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Protease\u2010activated receptor\u20101 contributes to renal injury and interstitial fibrosis during chronic obstructive nephropathy"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1103-7875","authenticated-orcid":false,"given":"Maaike","family":"Waasdorp","sequence":"first","affiliation":[{"name":"Center for Experimental and Molecular Medicine, Academic Medical Center Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis M.","family":"de Rooij","sequence":"additional","affiliation":[{"name":"Center for Experimental and Molecular Medicine, Academic Medical Center Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Florquin","sequence":"additional","affiliation":[{"name":"Pathology Academic Medical Center Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JanWillem","family":"Duitman","sequence":"additional","affiliation":[{"name":"Center for Experimental and Molecular Medicine, Academic Medical Center Amsterdam Amsterdam The Netherlands"},{"name":"D\u00e9partement Hospitalo\u2010Universitaire FIRE (Fibrosis, Inflammation and Remodeling) and LabEx Inflamex Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9 Paris France"},{"name":"Physiopathologie Et Epid\u00e9miologie Des Maladies Respiratoires, Medical School Xavier Bichat, Inserm UMR1152 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Arnold","family":"Spek","sequence":"additional","affiliation":[{"name":"Center for Experimental and Molecular Medicine, Academic Medical Center Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,11,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00041552-200003000-00006"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64327-1"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215518"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.6A7157.2007"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002277"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.11.007"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH12-11-0854"},{"key":"e_1_2_8_9_1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0031-6997(24)01493-5","article-title":"Proteinase\u2010activated receptors","volume":"53","author":"Macfarlane SR","year":"2001","journal-title":"Pharmacol Rev"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24165"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3109\/01902148.2013.820809"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006080886"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2014.00027"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62354-1"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfw175"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00444.2007"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2015.177"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep33030"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2013.127"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000115703.30835.96"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0014386"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrep.2017.03.009"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20161031"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-29008-2"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.7A7287.2007"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3218"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6095"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3902"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090517"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.28726"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2003.6"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22249"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1177\/1074248413485434"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjcmm.14028","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.14028","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T06:43:48Z","timestamp":1775285028000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.14028"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,28]]},"references-count":32,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["10.1111\/jcmm.14028"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.14028","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,28]]},"assertion":[{"value":"2018-06-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}