{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:22:10Z","timestamp":1792178530925,"version":"4.4.0"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T00:00:00Z","timestamp":1605052800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["19K08484"],"award-info":[{"award-number":["19K08484"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005865","name":"Mochida Memorial Foundation for Medical and Pharmaceutical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Increased transforming growth factor-\u03b2 (TGF-\u03b2) signaling contributes to the pathophysiology of aortic aneurysm in Marfan syndrome (MFS). Recent reports indicate that a small but significant number of inflammatory cells are infiltrated into the aortic media and adventitia in MFS. However, little is known about the contribution of myeloid cells to aortic aneurysmal formation. In this study, we ablated the TGF-\u03b2 type II receptor gene<jats:italic>Tgfbr2<\/jats:italic>in myeloid cells of<jats:italic>Fbn1<\/jats:italic><jats:sup><jats:italic>C1039G\/+<\/jats:italic><\/jats:sup>MFS mice (<jats:italic>Fbn1<\/jats:italic><jats:sup><jats:italic>C1039G\/+<\/jats:italic><\/jats:sup>;<jats:italic>LysM-Cre\/+<\/jats:italic>;<jats:italic>Tgfbr2<\/jats:italic><jats:sup><jats:italic>fl\/fl<\/jats:italic><\/jats:sup>mice, hereinafter called<jats:italic>Fbn1<\/jats:italic><jats:sup><jats:italic>C1039G\/+<\/jats:italic><\/jats:sup>;<jats:italic>Tgfbr2<\/jats:italic><jats:sup><jats:italic>MyeKO<\/jats:italic><\/jats:sup>) and evaluated macrophage infiltration and TGF-\u03b2 signaling in the aorta. Aneurysmal formation with fragmentation and disarray of medial elastic fibers observed in MFS mice was significantly ameliorated in<jats:italic>Fbn1<\/jats:italic><jats:sup><jats:italic>C1039G\/+<\/jats:italic><\/jats:sup>;<jats:italic>Tgfbr2<\/jats:italic><jats:sup><jats:italic>MyeKO<\/jats:italic><\/jats:sup>mice. In the aorta of<jats:italic>Fbn1<\/jats:italic><jats:sup><jats:italic>C1039G\/+<\/jats:italic><\/jats:sup>;<jats:italic>Tgfbr2<\/jats:italic><jats:sup><jats:italic>MyeKO<\/jats:italic><\/jats:sup>mice, both canonical and noncanonical TGF-\u03b2 signals were attenuated and the number of infiltrated F4\/80-positive macrophages was significantly reduced.<jats:italic>In vitro<\/jats:italic>, TGF-\u03b2 enhanced the migration capacity of RAW264.7 macrophages. These findings suggest that TGF-\u03b2 signaling in myeloid cells promotes aortic aneurysmal formation and its inhibition might be a novel therapeutic target in MFS.<\/jats:p>","DOI":"10.1371\/journal.pone.0239908","type":"journal-article","created":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T18:22:44Z","timestamp":1605118964000},"page":"e0239908","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Inhibition of transforming growth factor-\u03b2 signaling in myeloid cells ameliorates aortic aneurysmal formation in Marfan syndrome"],"prefix":"10.1371","volume":"15","author":[{"given":"Hironori","family":"Hara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4480-0862","authenticated-orcid":true,"given":"Sonoko","family":"Maemura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4818-3347","authenticated-orcid":true,"given":"Norifumi","family":"Takeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Yagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaaki","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mutsuo","family":"Harada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruhiro","family":"Toko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsubasa","family":"Kanaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Ijichi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold 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