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Evidence for increased OGFr in the epithelium included a three-fold increase in OGFr binding activity, as well as significant increases in OGFr protein, as monitored by semiquantitative immunohistochemistry. DNA synthesis in target epithelium, including cornea, tongue, and skin of transgenic mice was decreased 41% to 80% from wild-type littermates; the liver, a nonepithelial organ, was not altered. Decreased DNA synthesis in corneal epithelium induced by transgenic expression of OGFr was further reduced by treatment with exogenous OGF but reversed by exposure to the opioid antagonist, naloxone. The number of cell layers in both epidermis and cornea of OGFrTG\/K5-tTA animals was reduced nearly 45% from wild-type mice. Full-thickness wounds in mice overexpressing OGFr healed 37% to 75% slower than wild-type littermates. These data demonstrate for the first time that stable genetic amplification of OGFr downregulates homeostatic cell proliferation, as well as pathophysiological processes with respect to wound repair. These mice also can serve as a valuable model to dissect the mechanism of OGF-OGFr action and may be important in understanding the etiology, pathogenesis, and treatment of epithelium-related diseases.<\/jats:p>","DOI":"10.1152\/ajpregu.00670.2011","type":"journal-article","created":{"date-parts":[[2012,2,16]],"date-time":"2012-02-16T07:53:25Z","timestamp":1329378805000},"page":"R1084-R1090","source":"Crossref","is-referenced-by-count":13,"title":["Targeted overexpression of OGFr in epithelium of transgenic mice suppresses cell proliferation and impairs full-thickness wound closure"],"prefix":"10.1152","volume":"302","author":[{"given":"Patricia J.","family":"McLaughlin","sequence":"first","affiliation":[{"name":"Departments of 1Neural and Behavioral Sciences and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara L.","family":"Keiper","sequence":"additional","affiliation":[{"name":"Departments of 1Neural and Behavioral Sciences 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