{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T22:24:13Z","timestamp":1776983053496,"version":"3.51.4"},"reference-count":43,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:00:00Z","timestamp":1666310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"S\u00e3o Paulo Research Foundation","award":["2018\/00415-0"],"award-info":[{"award-number":["2018\/00415-0"]}]},{"name":"S\u00e3o Paulo Research Foundation","award":["2018\/20403-6"],"award-info":[{"award-number":["2018\/20403-6"]}]},{"name":"S\u00e3o Paulo Research Foundation","award":["2021\/13220-5"],"award-info":[{"award-number":["2021\/13220-5"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cutaneous fibrosis is one of the main features of systemic sclerosis (SSc). Recent findings correlated abnormal collagen V (Col V) deposition in dermis with skin thickening and disease activity in SSc. Considering that Col V is an important regulator of collagen fibrillogenesis, understanding the role of Col V in the first two years of the skin fibrosis in SSc (early SSc) can help to determine new targets for future treatments. In this study, we analyzed the morphological, ultrastructural and molecular features of \u03b11(V) and \u03b12(V) chains and the expression of their coding genes COL5A1 and COL5A2 in collagen fibrillogenesis in early-SSc. Skin biopsies were obtained from seven consecutive treatment-na\u00efve patients with SSc-related fibrosis and four healthy controls. Our data showed increased \u03b11(V) and \u03b12(V) chain expression in the reticular dermis of early-SSc patients; however, immunofluorescence and ultrastructural immunogold staining determined a significant decreased expression of the \u03b11(V) chain along the dermoepidermal junction in the papillary dermis from early-SSc-patients in relation to the control (12.77 \u00b1 1.34 vs. 66.84 \u00b1 3.36; p &lt; 0.0001). The immunoblot confirmed the decreased expression of the \u03b11(V) chain by the cutaneous fibroblasts of early-SSc, despite the increased COL5A1 and COL5A2 gene expression. In contrast, the \u03b12(V) chain was overexpressed in the small vessels (63.18 \u00b1 3.56 vs. 12.16 \u00b1 0.81; p &lt; 0.0001) and capillaries (60.88 \u00b1 5.82 vs. 15.11 \u00b1 3.80; p &lt; 0.0001) in the reticular dermis of early-SSc patients. Furthermore, COLVA2 siRNA in SSc cutaneous fibroblasts resulted in a decreased \u03b11(V) chain expression. These results highlight an intense decrease in the \u03b11(V) chain along the dermoepidermal junction, suggesting an altered molecular histoarchitecture in the SSc papillary dermis, with a possible decrease in the expression of the \u03b11(V)3 homotrimeric isoform, which could interfere with the thickening and cutaneous fibrosis related to SSc.<\/jats:p>","DOI":"10.3390\/ijms232012654","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T04:40:36Z","timestamp":1666586436000},"page":"12654","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Collagen V \u03b11 Chain Decrease in Papillary Dermis from Early Systemic Sclerosis: A New Proposal in Cutaneous Fibrosis Molecular Structure"],"prefix":"10.3390","volume":"23","author":[{"given":"Jymenez","family":"de Morais","sequence":"first","affiliation":[{"name":"Division of Rheumatology (LIM 17), Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Paula P.","family":"Velosa","sequence":"additional","affiliation":[{"name":"Division of Rheumatology (LIM 17), Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priscila C.","family":"Andrade","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise","family":"Frediani","sequence":"additional","affiliation":[{"name":"Discipline of Clinical Emergency (LIM 51), Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2469-9744","authenticated-orcid":false,"given":"Solange","family":"Carrasco","sequence":"additional","affiliation":[{"name":"Division of Rheumatology (LIM 17), Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zelita A. de Jesus","family":"Queiroz","sequence":"additional","affiliation":[{"name":"Division of Rheumatology (LIM 17), Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patr\u00edcia","family":"Martin","sequence":"additional","affiliation":[{"name":"Division of Rheumatology (LIM 17), Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata F.","family":"Saito","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Oncology (LIM24), Department of Radiology and Oncology, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"},{"name":"Instituto do C\u00e2ncer do Estado de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vit\u00f3ria","family":"Elias","sequence":"additional","affiliation":[{"name":"Division of Rheumatology (LIM 17), Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3306-9699","authenticated-orcid":false,"given":"Cl\u00e1udia","family":"Goldenstein-Schainberg","sequence":"additional","affiliation":[{"name":"Division of Rheumatology (LIM 17), Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0342-8726","authenticated-orcid":false,"given":"Roger","family":"Chammas","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Oncology (LIM24), Department of Radiology and Oncology, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"},{"name":"Instituto do C\u00e2ncer do Estado de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Percival D.","family":"Sampaio-Barros","sequence":"additional","affiliation":[{"name":"Division of Rheumatology (LIM 17), Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9732-5853","authenticated-orcid":false,"given":"Vera L.","family":"Capelozzi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walcy R.","family":"Teodoro","sequence":"additional","affiliation":[{"name":"Division of Rheumatology (LIM 17), Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1016\/S0140-6736(17)30933-9","article-title":"Systemic sclerosis","volume":"390","author":"Denton","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"137","DOI":"10.5301\/jsrd.5000249","article-title":"Pathogenesis of systemic sclerosis: Recent insights of molecular and cellular mechanisms 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