{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:57:34Z","timestamp":1790636254654,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T00:00:00Z","timestamp":1636070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50HD103555"],"award-info":[{"award-number":["P50HD103555"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI036211"],"award-info":[{"award-number":["AI036211"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA125123"],"award-info":[{"award-number":["CA125123"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK056338"],"award-info":[{"award-number":["DK056338"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Rolanette and Berdon Lawrence Bone Disease Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Type V collagen is a regulatory fibrillar collagen essential for type I collagen fibril nucleation and organization and its deficiency leads to structurally abnormal extracellular matrix (ECM). Haploinsufficiency of the Col5a1 gene encoding \u03b1(1) chain of type V collagen is the primary cause of classic Ehlers\u2013Danlos syndrome (EDS). The mechanisms by which this initial insult leads to the spectrum of clinical presentation are not fully understood. Using transcriptome analysis of skin and Achilles tendons from Col5a1 haploinsufficient (Col5a1+\/\u2212) mice, we recognized molecular alterations associated with the tissue phenotypes. We identified dysregulation of ECM components including thrombospondin-1, lysyl oxidase, and lumican in the skin of Col5a1+\/\u2212 mice when compared with control. We also identified upregulation of transforming growth factor \u03b21 (Tgf-\u03b2) in serum and increased expression of pSmad2 in skin from Col5a1+\/\u2212 mice, suggesting Tgf-\u03b2 dysregulation is a contributor to abnormal wound healing and atrophic scarring seen in classic EDS. Together, these findings support altered matrix to cell signaling as a component of the pathogenesis of the tissue phenotype in classic EDS and point out potential downstream signaling pathways that may be targeted for the treatment of this disease.<\/jats:p>","DOI":"10.1093\/hmg\/ddab323","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T23:49:21Z","timestamp":1636156161000},"page":"1325-1335","source":"Crossref","is-referenced-by-count":14,"title":["Molecular alterations due to <i>Col5a1<\/i> haploinsufficiency in a mouse model of classic Ehlers\u2013Danlos syndrome"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0356-6889","authenticated-orcid":false,"given":"Keren","family":"Machol","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor college of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urszula","family":"Polak","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor college of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Weisz-Hubshman","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor college of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Wen","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor college of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor college of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Ming","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor college of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Chen-Evenson","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor college of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Ann E","family":"Weis","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Sports Medicine, University of Washington Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas R","family":"Keene","sequence":"additional","affiliation":[{"name":"Micro-Imaging Center, Shriners Hospital for Children, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R","family":"Eyre","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Sports Medicine, University of Washington Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan H","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor college of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,11,5]]},"reference":[{"key":"2022042214140722600_ref1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/ajmg.c.31548","article-title":"Ehlers-Danlos syndrome, classical type","volume":"175","author":"Bowen","year":"2017","journal-title":"Am. 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Rare Dis."},{"key":"2022042214140722600_ref3","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0968-4328(00)00043-3","article-title":"Type V collagen: heterotypic type I\/V collagen interactions in the regulation of fibril assembly","volume":"32","author":"Birk","year":"2001","journal-title":"Micron"},{"key":"2022042214140722600_ref4","doi-asserted-by":"crossref","first-page":"12888","DOI":"10.1074\/jbc.M511528200","article-title":"Murine model of the Ehlers-Danlos syndrome. col5a1 haploinsufficiency disrupts collagen fibril assembly at multiple stages","volume":"281","author":"Wenstrup","year":"2006","journal-title":"J. Biol. Chem."},{"key":"2022042214140722600_ref5","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/jcb.20024","article-title":"Reduced type I collagen utilization: a pathogenic mechanism in COL5A1 haplo-insufficient Ehlers-Danlos syndrome","volume":"92","author":"Wenstrup","year":"2004","journal-title":"J. Cell. 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