{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T16:28:00Z","timestamp":1774542480053,"version":"3.50.1"},"reference-count":74,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:00:00Z","timestamp":1728000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wisconsin Alumni Research Foundation, the School of Pharmacy at University of Wisconsin-Madison","award":["P30 AR066524"],"award-info":[{"award-number":["P30 AR066524"]}]},{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)","award":["P30 AR066524"],"award-info":[{"award-number":["P30 AR066524"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The skin epidermis provides a barrier that is imperative for preventing transepidermal water loss (TEWL) and protecting against environmental stimuli. The underlying molecular mechanisms for regulating barrier functions and sustaining its integrity remain unclear. ROR\u03b1 is a nuclear receptor highly expressed in the epidermis of normal skin. Clinical studies showed that the epidermal ROR\u03b1 expression is significantly reduced in the lesions of multiple inflammatory skin diseases. In this study, we investigate the central roles of ROR\u03b1 in stabilizing skin barrier function using mice with an epidermis-specific Rora gene deletion (RoraEKO). While lacking spontaneous skin lesions or dermatitis, RoraEKO mice exhibited an elevated TEWL rate and skin characteristics of barrier dysfunction. Immunostaining and Western blot analysis revealed low levels of cornified envelope proteins in the RoraEKO epidermis, suggesting disturbed late epidermal differentiation. In addition, an RNA-seq analysis showed the altered expression of genes related to \u201ckeratinization\u201d and \u201clipid metabolism\u201d in ROR\u03b1 deficient epidermis. A lipidomic analysis further uncovered an aberrant ceramide composition in the RoraEKO epidermis. Importantly, epidermal Rora ablation greatly exaggerated percutaneous allergic inflammatory responses to oxazolone in an allergic contact dermatitis (ACD) mouse model. Our results substantiate the essence of epidermal ROR\u03b1 in maintaining late keratinocyte differentiation and normal barrier function while suppressing cutaneous inflammation.<\/jats:p>","DOI":"10.3390\/ijms251910698","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T07:49:42Z","timestamp":1728028182000},"page":"10698","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Epidermal ROR\u03b1 Maintains Barrier Integrity and Prevents Allergic Inflammation by Regulating Late Differentiation and Lipid Metabolism"],"prefix":"10.3390","volume":"25","author":[{"given":"Xiangmei","family":"Hua","sequence":"first","affiliation":[{"name":"School of Pharmacy, The University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria K.","family":"Ficaro","sequence":"additional","affiliation":[{"name":"School of Pharmacy, The University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole L.","family":"Wallace","sequence":"additional","affiliation":[{"name":"School of Pharmacy, The University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Dai","sequence":"additional","affiliation":[{"name":"School of Pharmacy, The University of Wisconsin, Madison, WI 53705, USA"},{"name":"Carbone Cancer Center, The University of Wisconsin, Madison, WI 53705, USA"},{"name":"Skin Disease Research Center, The University of Wisconsin, Madison, WI 53705, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.bbalip.2013.11.007","article-title":"Role of lipids in the formation and maintenance of the cutaneous permeability barrier","volume":"1841","author":"Feingold","year":"2014","journal-title":"Biochim. 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