{"id":76969,"date":"2026-09-22T06:04:25","date_gmt":"2026-09-22T04:04:25","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/09\/22\/targeting-epha2-with-a-novel-efna3-mimetic-peptide-enhances-vaginal-epithelial-barrier-function-running-title-efna3-map-enhancing-the-vaginal-epithelial-barrier-rodolfo-d-vicetti-miguel\/"},"modified":"2026-09-22T06:04:25","modified_gmt":"2026-09-22T04:04:25","slug":"targeting-epha2-with-a-novel-efna3-mimetic-peptide-enhances-vaginal-epithelial-barrier-function-running-title-efna3-map-enhancing-the-vaginal-epithelial-barrier-rodolfo-d-vicetti-miguel","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/09\/22\/targeting-epha2-with-a-novel-efna3-mimetic-peptide-enhances-vaginal-epithelial-barrier-function-running-title-efna3-map-enhancing-the-vaginal-epithelial-barrier-rodolfo-d-vicetti-miguel\/","title":{"rendered":"Targeting EphA2 with a novel EFNA3-mimetic peptide enhances vaginal epithelial barrier function: Running title: EFNA3-MAP enhancing the vaginal epithelial barrier. Rodolfo D Vicetti Miguel"},"content":{"rendered":"<div>\n<p><b>Mucosal Immunol<\/b>. 2026 Sep 21:100406. doi: 10.1016\/j.mucimm.2026.100406. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Barrier protection provided by vaginal stratified squamous epithelium (SSE) is supported by estrogen (E)-mediated stimulation of ephrin-Eph signaling that promote desmosome expression and function. Conversely, loss of E induced by use of the contraceptive depot-medroxyprogesterone acetate (DMPA) or menopause reduces desmosome expression and weakens this epithelial barrier. We previously reported treating mice with DMPA lowers expression of the desmosomal cadherin desmoglein-1 (DSG1) in vaginal SSE by dampening EFNA3-mediated signaling whereas these effects are partially reversed by intravaginal administration of recombinant EFNA3 (rEFNA3) protein. Herein we extended these results, developing an EFNA3-mimetic agonist peptide (EFNA3-MAP) that engages the EphA2 receptor in vitro. In vivo, EFNA3-MAP penetrated vaginal SSE more effectively than rEFNA3 and restored DSG1 levels and vaginal epithelial thickness in DMPA-treated mice. It also reduced susceptibility of these mice to genital infection with bacterial and viral pathogens. In separate studies, we showed that EFNA3-MAP bioactivity depended on G-H loop aromatic residues and EphA2 engagement and that topical EFNA3-MAP restored vaginal epithelial thickness and DSG1 expression in DMPA-treated rhesus macaques. Together, current studies establish EFNA3-EphA2 signaling as a key regulator of vaginal SSE health and offer strong rationale to explore if EFNA3-MAP similarly enhances cutaneous SSE barrier function.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42767373\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101299742&amp;ff=20260922000424&amp;v=2.20.1\">42767373<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1016\/j.mucimm.2026.100406\">10.1016\/j.mucimm.2026.100406<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Mucosal Immunol. 2026 Sep 21:100406. doi: 10.1016\/j.mucimm.2026.100406. Online ahead of print. ABSTRACT Barrier protection provided by vaginal stratified squamous epithelium (SSE) is supported by estrogen (E)-mediated stimulation of ephrin-Eph signaling that promote desmosome expression and function. Conversely, loss of E induced by use of the contraceptive depot-medroxyprogesterone acetate (DMPA) or menopause reduces desmosome expression and &#8230; <a title=\"Targeting EphA2 with a novel EFNA3-mimetic peptide enhances vaginal epithelial barrier function: Running title: EFNA3-MAP enhancing the vaginal epithelial barrier. Rodolfo D Vicetti Miguel\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/09\/22\/targeting-epha2-with-a-novel-efna3-mimetic-peptide-enhances-vaginal-epithelial-barrier-function-running-title-efna3-map-enhancing-the-vaginal-epithelial-barrier-rodolfo-d-vicetti-miguel\/\" aria-label=\"Read more about Targeting EphA2 with a novel EFNA3-mimetic peptide enhances vaginal epithelial barrier function: Running title: EFNA3-MAP enhancing the vaginal epithelial barrier. Rodolfo D Vicetti Miguel\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[57,42],"tags":[],"class_list":["post-76969","post","type-post","status-publish","format-standard","hentry","category-mucosal-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/76969","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=76969"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/76969\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=76969"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=76969"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=76969"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}