{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T05:08:52Z","timestamp":1791954532598,"version":"4.3.4"},"reference-count":28,"publisher":"American Society for Clinical Investigation","issue":"24","license":[{"start":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T00:00:00Z","timestamp":1703203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["5R21AR077769-02"],"award-info":[{"award-number":["5R21AR077769-02"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Stepping Strong Foundation","award":["Innovator Award"],"award-info":[{"award-number":["Innovator Award"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["1K08AR082031-01"],"award-info":[{"award-number":["1K08AR082031-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,22]]},"abstract":"<jats:p>\n                    Secondary lymphedema occurs in up to 20% of patients after lymphadenectomy performed for the surgical management of tumors involving the breast, prostate, uterus, and skin. Patients develop progressive edema of the affected extremity due to retention of protein-rich lymphatic fluid. Despite compression therapy, patients progress to chronic lymphedema in which noncompressible fibrosis and adipose tissue are deposited within the extremity. The presence of fibrosis led to our hypothesis that rosiglitazone, a PPAR\u03b3 agonist that inhibits fibrosis, would reduce fibrosis in a mouse model of secondary lymphedema after hind limb lymphadenectomy. In vivo, rosiglitazone reduced fibrosis in the hind limb after lymphadenectomy. Our findings verified that rosiglitazone reestablished the adipogenic features of TGF-\u03b21\u2013treated mesenchymal cells in vitro. Despite this, rosiglitazone led to a reduction in adipose tissue deposition. Single-cell RNA-Seq data obtained from human tissues and flow cytometric and histological evaluation of mouse tissues demonstrated increased presence of PDGFR\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    cells in lymphedema; human tissue analysis verified these cells have the capacity for adipogenic and fibrogenic differentiation. Upon treatment with rosiglitazone, we noted a reduction in the overall quantity of PDGFR\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    cells and LipidTOX\n                    <jats:sup>+<\/jats:sup>\n                    cells. Our findings provide a framework for treating secondary lymphedema as a condition of fibrosis and adipose tissue deposition, both of which, paradoxically, can be prevented with a pro-adipogenic agent.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.165324","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T14:00:44Z","timestamp":1703167244000},"source":"Crossref","is-referenced-by-count":18,"title":["PPAR\u03b3 agonist treatment reduces fibroadipose tissue in secondary lymphedema by exhausting fibroadipogenic PDGFR\u03b1+ mesenchymal cells"],"prefix":"10.1172","volume":"8","author":[{"given":"Ziyu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Surgery, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Department of Bone and Joint Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soheila Ali Akbari","family":"Ghavimi","sequence":"additional","affiliation":[{"name":"Department of Surgery, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengfan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Surgery, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"McNamara","sequence":"additional","affiliation":[{"name":"Rutgers University, Rutgers, New Jersey, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Barreiro","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Maridas","sequence":"additional","affiliation":[{"name":"Harvard School of Dental Medicine, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radomir","family":"Kratchmarov","sequence":"additional","affiliation":[{"name":"Division of Allergy and Clinical Immunology, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Siegel","sequence":"additional","affiliation":[{"name":"Department of Surgery, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Djeddi","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gutierrez-Arcelus","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick J.","family":"Brennan","sequence":"additional","affiliation":[{"name":"Division of Allergy and Clinical Immunology, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy P.","family":"Padera","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"von Andrian","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5717-697X","authenticated-orcid":true,"given":"Babak","family":"Mehrara","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arin K.","family":"Greene","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7583-9228","authenticated-orcid":true,"given":"C. 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