{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:01:35Z","timestamp":1792144895750,"version":"4.4.0"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,3,27]],"date-time":"2015-03-27T00:00:00Z","timestamp":1427414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Accumulation of myofibroblasts in fibrotic skin is a hallmark of systemic sclerosis (SSc; scleroderma), but the origins of these cells remain unknown. Because loss of intradermal adipose tissue is a consistent feature of cutaneous fibrosis, we sought to examine the hypothesis that myofibroblasts populating fibrotic dermis derive from adipocytic progenitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed genetic fate mapping studies to investigate the loss of intradermal adipose tissue and its potential role in fibrosis in mice with bleomycin\u2010induced scleroderma. Modulation of adipocytic phenotypes ex vivo was investigated in adipose tissue\u2013derived cells in culture.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A striking loss of intradermal adipose tissue and its replacement with fibrous tissue were consistently observed in mice with bleomycin\u2010induced fibrosis. Loss of adipose tissue and a decline in the expression of canonical adipogenic markers in lesional skin preceded the onset of dermal fibrosis and expression of fibrogenic markers. Ex vivo, subcutaneous adipocytes were driven by transforming growth factor \u03b2 to preferentially undergo fibrogenic differentiation. Cell fate mapping studies in mice with the adiponectin promoter\u2013driven Cre recombinase transgenic construct indicated that adiponectin\u2010positive progenitors that are normally confined to the intradermal adipose tissue compartment were distributed throughout the lesional dermis over time, lost their adipocytic markers, and expressed myofibroblast markers in bleomycin\u2010treated mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These observations establish a novel link between intradermal adipose tissue loss and dermal fibrosis and demonstrate that adiponectin\u2010positive intradermal progenitors give rise to dermal myofibroblasts. Adipose tissue loss and adipocyte\u2013myofibroblast transition might be primary events in the pathogenesis of cutaneous fibrosis that represent novel potential targets for therapeutic intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.38990","type":"journal-article","created":{"date-parts":[[2014,12,10]],"date-time":"2014-12-10T10:34:27Z","timestamp":1418207667000},"page":"1062-1073","source":"Crossref","is-referenced-by-count":330,"title":["Myofibroblasts in Murine Cutaneous Fibrosis Originate From Adiponectin\u2010Positive Intradermal Progenitors"],"prefix":"10.1002","volume":"67","author":[{"given":"Roberta Goncalves","family":"Marangoni","sequence":"first","affiliation":[{"name":"Northwestern University Feinberg School of Medicine Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin D.","family":"Korman","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wei","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammara A.","family":"Wood","sequence":"additional","affiliation":[{"name":"Geisel School of Medicine at Dartmouth, Medical School Hanover New Hampshire"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren V.","family":"Graham","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Whitfield","sequence":"additional","affiliation":[{"name":"Geisel School of Medicine at Dartmouth, Medical School Hanover New Hampshire"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp 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