{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:50:00Z","timestamp":1790862600192,"version":"4.1.0"},"reference-count":97,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T00:00:00Z","timestamp":1628640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01-BX003762"],"award-info":[{"award-number":["I01-BX003762"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01 CX002046"],"award-info":[{"award-number":["I01 CX002046"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["IK2CX001019"],"award-info":[{"award-number":["IK2CX001019"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006976","name":"Lilly Endowment","doi-asserted-by":"publisher","award":["Indiana Genomic Initiative at Indiana University"],"award-info":[{"award-number":["Indiana Genomic Initiative at Indiana University"]}],"id":[{"id":"10.13039\/100006976","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Both agonist studies and loss-of-function models indicate that PPAR\u03b3 plays an important role in cutaneous biology. Since PPAR\u03b3 has a high level of basal activity, we hypothesized that epidermal PPAR\u03b3 would regulate normal homeostatic processes within the epidermis. In this current study, we performed mRNA sequencing and differential expression analysis of epidermal scrapings from knockout mice and wildtype littermates. Pparg-\/-epi mice exhibited a 1.5-fold or greater change in the expression of 11.8% of 14,482 identified transcripts. Up-regulated transcripts included those for a large number of cytokines\/chemokines and their receptors, as well as genes associated with inflammasome activation and keratinization. Several of the most dramatically up-regulated pro-inflammatory genes in Pparg-\/-epi mouse skin included Igfl3, 2610528A11Rik, and Il1f6. RT-PCR was performed from RNA obtained from non-lesional full-thickness skin and verified a marked increase in these transcripts, as well as transcripts for Igflr1, which encodes the receptor for Igfl3, and the 2610528A11Rik receptor (Gpr15). Transcripts for Il4 were detected in Pparg-\/-epi mouse skin, but transcripts for Il17 and Il22 were not detected. Down-regulated transcripts included sebaceous gland markers and a number of genes associated with lipid barrier formation. The change in these transcripts correlates with an asebia phenotype, increased transepidermal water loss, alopecia, dandruff, and the appearance of spontaneous inflammatory skin lesions. Histologically, non-lesional skin showed hyperkeratosis, while inflammatory lesions were characterized by dermal inflammation and epidermal acanthosis, spongiosis, and parakeratosis. In conclusion, loss of epidermal Pparg alters a substantial set of genes that are associated with cutaneous inflammation, keratinization, and sebaceous gland function. The data indicate that epidermal PPAR\u03b3 plays an important role in homeostatic epidermal function, particularly epidermal differentiation, barrier function, sebaceous gland development and function, and inflammatory signaling.<\/jats:p>","DOI":"10.3390\/ijms22168634","type":"journal-article","created":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T08:35:52Z","timestamp":1628670952000},"page":"8634","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Epidermal PPAR\u03b3 Is a Key Homeostatic Regulator of Cutaneous Inflammation and Barrier Function in Mouse Skin"],"prefix":"10.3390","volume":"22","author":[{"given":"Raymond L.","family":"Konger","sequence":"first","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, IN 46202, USA"},{"name":"Department of Pathology & Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"The Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethel","family":"Derr-Yellin","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, IN 46202, USA"},{"name":"Department of Pathology & Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7872-0540","authenticated-orcid":false,"given":"Teresa A.","family":"Zimmers","sequence":"additional","affiliation":[{"name":"The Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terrence","family":"Katona","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Xuei","sequence":"additional","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2699-626X","authenticated-orcid":false,"given":"Yunlong","family":"Liu","sequence":"additional","affiliation":[{"name":"The Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Ming","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Ed Ronald","family":"Simpson","sequence":"additional","affiliation":[{"name":"Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Turner","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Dermatology, Richard L. 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