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In a humanized skin mouse model that maintains interfollicular epidermal melanocytes, we found that forskolin, a small molecule that directly activates adenylyl cyclase and promotes <jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content> generation, up\u2010regulated epidermal eumelanin accumulation in fair\u2010skinned melanocortin\u20101\u2010receptor (<jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>c1r)\u2010defective animals. Forskolin\u2010induced pigmentation was associated with a reproducible expansion of epidermal thickness irrespective of melanization or the presence of epidermal melanocytes. Rather, forskolin\u2010enhanced epidermal thickening was mediated through increased keratinocyte proliferation, indirectly through secreted factor(s) from cutaneous fibroblasts. We identified keratinocyte growth factor (<jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>gf) as a forskolin\u2010induced fibroblast\u2010derived cytokine that promoted keratinocyte proliferation, as forskolin induced <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>gf expression both in the skin and in primary fibroblasts. Lastly, we found that even in the absence of pigmentation, forskolin\u2010induced epidermal thickening significantly diminished the amount of <jats:styled-content style=\"fixed-case\">UV\u2010A<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">UV\u2010B<\/jats:styled-content> that passed through whole skin and reduced the amount of <jats:styled-content style=\"fixed-case\">UV\u2010B<\/jats:styled-content>\u2010associated epidermal sunburn cells. These findings suggest the possibility of pharmacologic\u2010induced epidermal thickening as a novel <jats:styled-content style=\"fixed-case\">UV<\/jats:styled-content>\u2010protective therapeutic intervention, particularly for individuals with defects in pigmentation and adaptive melanization.<\/jats:p>","DOI":"10.1111\/exd.12012","type":"journal-article","created":{"date-parts":[[2012,8,20]],"date-time":"2012-08-20T08:33:15Z","timestamp":1345451595000},"page":"771-777","source":"Crossref","is-referenced-by-count":59,"title":["Pigment\u2010independent <scp>cAMP<\/scp>\u2010mediated epidermal thickening protects against cutaneous <scp>UV<\/scp> injury by keratinocyte proliferation"],"prefix":"10.1111","volume":"21","author":[{"given":"Timothy L.","family":"Scott","sequence":"first","affiliation":[{"name":"Department of Pediatrics and the Graduate Center for Toxicology, Markey Cancer Center University of Kentucky College of Medicine Lexington KY 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