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Additionally, the pathobiology of pathologic scars remains poorly understood. We aim at investigating the impact of TEM1 (also known as endosialin or CD248), which is a glycosylated type I transmembrane protein, on development of pathologic scars.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To investigate the expression of TEM1, we utilized immunofluorescence staining, Western blotting, and single-cell RNA-sequencing (scRNA-seq) techniques. We conducted in vitro cell culture experiments and an in vivo stretch-induced scar mouse model to study the involvement of TEM1 in TGF-\u03b2-mediated responses in pathologic scars.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The levels of the protein TEM1 are elevated in both hypertrophic scars and keloids in comparison to normal skin. A re-analysis of scRNA-seq datasets reveals that a major profibrotic subpopulation of keloid and hypertrophic scar fibroblasts greatly expresses TEM1, with expression increasing during fibroblast activation. TEM1 promotes activation, proliferation, and ECM production in human dermal fibroblasts by enhancing TGF-\u03b21 signaling through binding with and stabilizing TGF-\u03b2 receptors. Global deletion of\n                      <jats:italic>Tem1<\/jats:italic>\n                      markedly reduces the amount of ECM synthesis and inflammation in a scar in a mouse model of stretch-induced pathologic scarring. The intralesional administration of ontuxizumab, a humanized IgG monoclonal antibody targeting TEM1, significantly decreased both the size and collagen density of keloids.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data indicate that TEM1 plays a role in pathologic scarring, with its synergistic effect on the TGF-\u03b2 signaling contributing to dermal fibroblast activation. Targeting TEM1 may represent a novel therapeutic approach in reducing the morbidity of pathologic scars.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12929-024-01001-0","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T22:02:43Z","timestamp":1705960963000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["TEM1\/endosialin\/CD248 promotes pathologic scarring and TGF-\u03b2 activity through its receptor stability in dermal fibroblasts"],"prefix":"10.1186","volume":"31","author":[{"given":"Yi-Kai","family":"Hong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsung-Lin","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Han","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Han","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Lun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Yi","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Han","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Shu","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Chu","family":"Ku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Ting","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Jer","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Wha","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guey-Yueh","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"McGrath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua-Lin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4365-4533","authenticated-orcid":false,"given":"Chao-Kai","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,23]]},"reference":[{"issue":"1","key":"1001_CR1","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1097\/DAD.0b013e3181d0c3ad","volume":"33","author":"AG Abdou","year":"2011","unstructured":"Abdou AG, Maraee AH, Al-Bara AM, Diab WM. 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Int J Mol Med. 2017;39(1):153\u20139.","journal-title":"Int J Mol Med"}],"container-title":["Journal of Biomedical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12929-024-01001-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12929-024-01001-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12929-024-01001-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T10:10:00Z","timestamp":1706004600000},"score":1,"resource":{"primary":{"URL":"https:\/\/jbiomedsci.biomedcentral.com\/articles\/10.1186\/s12929-024-01001-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,23]]},"references-count":99,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["1001"],"URL":"https:\/\/doi.org\/10.1186\/s12929-024-01001-0","relation":{},"ISSN":["1423-0127"],"issn-type":[{"value":"1423-0127","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,23]]},"assertion":[{"value":"6 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 January 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Human studies were approved by the Institutional Review Board of the National Cheng Kung University Hospital, based on the Declaration of Helsinki (NCKUH B-ER-105-008 and A-BR-109-037). Written consent was obtained from each patient before surgery. Animal studies were approved by the Institutional Animal Care and Use Committee of the Laboratory Animal Center, National Cheng Kung University, Tainan, Taiwan (IACUC No. 105119).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors state no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"12"}}