{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T03:52:03Z","timestamp":1779162723482,"version":"3.51.4"},"reference-count":27,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,1,2]],"date-time":"2013-01-02T00:00:00Z","timestamp":1357084800000},"content-version":"vor","delay-in-days":185,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Poor healing of DFUs (diabetic foot ulcers) is a major clinical problem that can be extremely debilitating and lead to lower limb amputation. In the normal acute wound, the Cx43 (connexin 43) gap junction protein is down\u2010regulated at the wound edge as a precursor to cell migration and healing. In fibroblasts from the human chronic DFU wound edge there was a striking and significant 10\u2010fold elevation of Cx43 protein, as well as a 6\u2010fold increase in N\u2010cadherin and a 2\u2010fold increase in ZO\u20101 (zonular occludin\u20101), compared with unwounded skin. In streptozotocin diabetic rats, Cx43 was found to be up\u2010regulated in intact dermal fibroblasts in direct proportion to blood glucose levels and increased 2\u2010fold further in response to wounding of the skin. To mimic diabetes, NIH 3T3 fibroblasts were cultured under different concentrations of glucose or mannitol and Cx43 protein intercellular communication and migration rates were determined. Cultures of fibroblasts in very high (40 mM) glucose conditions showed significantly elevated Cx43 protein levels, as shown by immunostaining and Western blotting, and significantly increasing gap junctional communication, as shown by dye transfer. In scratch wound\u2010healing assays, increased levels of Cx43 from high glucose resulted in repressed filopodial extensions and significantly slower migration rates than in either standard conditions (5.5 mM glucose) or the osmotic control of mannitol. Conversely, when glucose\u2010induced Cx43 up\u2010regulation was prevented with Cx43shRNA (Cx43 short\u2010hairpin RNA) transduction, the fibroblasts extended long filopodia and migrated significantly faster. Cx43 protein was up\u2010regulated in fibroblasts in DFUs as well as after high glucose exposure in culture which correlated with inhibition of fibroblast migration and is likely to contribute to impaired wound healing.<\/jats:p>","DOI":"10.1042\/cbi20110628","type":"journal-article","created":{"date-parts":[[2012,3,29]],"date-time":"2012-03-29T13:50:06Z","timestamp":1333029006000},"page":"661-667","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Overexpression of the gap junction protein Cx43 as found in diabetic foot ulcers can retard fibroblast migration"],"prefix":"10.1002","volume":"36","author":[{"given":"Ariadna","family":"Mendoza\u2010Naranjo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Cormie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio 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