{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T21:23:27Z","timestamp":1788557007013,"version":"build-2803163510"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,11,12]],"date-time":"2013-11-12T00:00:00Z","timestamp":1384214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100000629","name":"Age UK","doi-asserted-by":"publisher","award":["358"],"award-info":[{"award-number":["358"]}],"id":[{"id":"10.13039\/501100000629","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Age\u2010related defects in fibroblast differentiation were previously shown to be associated with impaired hyaluronan synthase 2 (<jats:styled-content style=\"fixed-case\">HAS<\/jats:styled-content>2) and epidermal growth factor receptor (<jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>) function, with both required for normal fibroblast functionality. In fibroblasts, transforming growth factor\u2010beta 1 (<jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b21)\u2010dependent phenotypic activation uses two distinct but co\u2010operating pathways that involve <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b2 receptor (<jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b2<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>)\/<jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>mad2 activation and <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>\u2010mediated <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>44\u2010<jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content> co\u2010localization and signalling through extracellular signal\u2010regulated kinase 1\/2 (<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2). The <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>\u2010mediated <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>44\u2010<jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content> pathway was found to be compromised with <jats:italic>in vitro<\/jats:italic> aging, through loss of <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content> expression and a reduced movement of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>44 throughout the cellular membrane. Here, we also investigate the involvement of micro<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s (mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s) in age\u2010related loss of differentiation, through investigation of mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u20107 (mi<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u20107) regulation of the <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>\u2010mediated <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>\u2010signalling pathway. The transcription of mi<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u20107 was found to be upregulated in aged cells. In young cells, age\u2010related loss of differentiation could be mimicked through transfection of pre\u2010mi<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u20107, and in aged cells, could be reversed through transfection of locked nucleic acids (<jats:styled-content style=\"fixed-case\">LNA<\/jats:styled-content>) targeting mi<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u20107. Additionally, mi<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u20107 was found to be involved in the regulation of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>44 membrane motility, which was downregulated in instances of mi<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u20107 upregulation, and partially restorable through either mi<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u20107 inhibition or <jats:styled-content style=\"fixed-case\">HAS<\/jats:styled-content>2 overexpression. The altered dynamics of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>44 in the cell membrane demonstrated a further action of mi<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u20107 in regulating the <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>\u2010dependent <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>44\/<jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content> pathway. We explain this novel mechanism of age\u2010associated functional consequence due to miR\u20107 upregulation and demonstrate that it is reversible; highlighting mi<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u20107 as a potential target for restoring the healing capabilities in chronic wounds in the elderly.<\/jats:p>","DOI":"10.1111\/acel.12167","type":"journal-article","created":{"date-parts":[[2013,10,17]],"date-time":"2013-10-17T15:59:14Z","timestamp":1382025554000},"page":"235-244","source":"Crossref","is-referenced-by-count":35,"title":["Micro<scp>RNA<\/scp>\u20107 inhibition rescues age\u2010associated loss of epidermal growth factor receptor and hyaluronan\u2010dependent differentiation in fibroblasts"],"prefix":"10.1111","volume":"13","author":[{"given":"Adam C.","family":"Midgley","sequence":"first","affiliation":[{"name":"Institute of Nephrology Institute of Molecular &amp; Experimental Medicine School of Medicine and Cardiff Institute of Tissue Engineering &amp; Repair University of Cardiff Heath Park Cardiff CF14 4XN UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Bowen","sequence":"additional","affiliation":[{"name":"Institute of Nephrology Institute of Molecular &amp; Experimental Medicine School of Medicine and Cardiff Institute of Tissue Engineering &amp; Repair University of Cardiff Heath Park Cardiff CF14 4XN UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aled O.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Institute of Nephrology Institute of Molecular &amp; Experimental Medicine School of Medicine and Cardiff Institute of Tissue Engineering &amp; Repair University of Cardiff Heath Park Cardiff CF14 4XN UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Steadman","sequence":"additional","affiliation":[{"name":"Institute of Nephrology Institute of Molecular &amp; Experimental Medicine School of Medicine and Cardiff Institute of Tissue Engineering &amp; Repair University of Cardiff Heath Park Cardiff CF14 4XN UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,11,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(99)00036-2"},{"issue":"1","key":"e_1_2_7_3_1","first-page":"1","article-title":"The effects of ageing on cutaneous wound healing in mammals","volume":"187","author":"Ashcroft GS","year":"1995","journal-title":"J. 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