{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:07:25Z","timestamp":1791234445793,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:00:00Z","timestamp":1599696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Systemic sclerosis is an autoimmune skin disease which is associated with inflammation and resulting skin fibrosis. Myofibroblasts are the key cell type associated with the fibrosis but how they are differentiated is not clear. DKK\u20101 is a Wnt antagonist that blocks Wnt\u2010mediated fibrosis and is reduced in fibrotic conditions. Thus, DKK\u20101 is a clear negative regulator of fibrosis in systemic sclerosis and its regulation is unknown. The aim of this work is to determine the levels of DKK\u20101 in serum and tissues of SSc and its regulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Skin biopsies were taken from early diffuse systemic sclerosis patients and healthy controls and DKK\u20101 measured by ELISA; serum was also isolated and DKK\u20101 quantified. DKK\u20101 was also measured by qRT\u2010PCR. MicroRNA33a\u20103p was measured by TaqMan PCR. miR mimics and controls were transfected into dermal fibroblasts. Bleomycin mouse model was employed and compared to vehicle control treated mice, and gene expression was employed for DKK\u20101 and various extracellular matrix genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>DKK\u20101 is reduced in SSc skin and fibroblasts but is not reduced in the circulation in patients. MicroRNA33a\u20103p regulates DKK\u20101 levels epigenetically and is significantly reduced in SSc cells and whole tissue. DKK\u20101 is also reduced in the bleomycin mouse model and pro\u2010fibrotic genes elevated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>DKK\u20101 is reduced in SSc cells and is regulated by miR33a\u20103p, and restoring DKK\u20101 levels through epigenetic means could be a therapeutic target in systemic sclerosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/exd.14136","type":"journal-article","created":{"date-parts":[[2020,6,27]],"date-time":"2020-06-27T11:25:07Z","timestamp":1593257107000},"page":"162-168","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Wnt antagonist DKK\u20101 levels in systemic sclerosis are lower in skin but not in blood and are regulated by microRNA33a\u20103p"],"prefix":"10.1111","volume":"30","author":[{"given":"John","family":"Henderson","sequence":"first","affiliation":[{"name":"Department of Applied Sciences Faculty of Health and Life Sciences Northumbria University Newcastle Upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Pryzborski","sequence":"additional","affiliation":[{"name":"Department of Biosciences Durham University Durham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Stratton","sequence":"additional","affiliation":[{"name":"Centre for Rheumatology and Connective Tissue Diseases University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7483-740X","authenticated-orcid":false,"given":"Steven","family":"O\u2019Reilly","sequence":"additional","affiliation":[{"name":"Department of Biosciences Durham University Durham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.13238"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.02.016"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11073"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0806188"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30933-9"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.122.6_suppl.286S"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31139"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-203995"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202544"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34424"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2010-0113OC"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30312"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-200568"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/35083081"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-203194"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38098"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22759"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1734"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(01)00290-1"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2019.02.001"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20170039"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-016-0929-x"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-019-2086-3"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1189123"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI81676"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.2337\/db11-0944"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.309528"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26604"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.131102"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2013.09.018"}],"container-title":["Experimental 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