{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:23:55Z","timestamp":1788276235964,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grants-in-Aid from the Japan Society for the Promotion of Science","award":["22H02263"],"award-info":[{"award-number":["22H02263"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Recently, we demonstrated that the alopecia observed in vitamin D receptor gene-deficient (Vdr-KO) rats is not seen in rats with a mutant VDR(R270L\/H301Q), which lacks ligand-binding ability, suggesting that the ligand-independent action of VDR plays a crucial role in maintaining the hair cycle. Since Vdr-KO rats also showed abnormalities in the skin, the relationship between alopecia and skin abnormalities was examined. To clarify the mechanism of actions of vitamin D and VDR in the skin, protein composition, and gene expression patterns in the skin were compared among Vdr-KO, Vdr-R270L\/H301Q, and wild-type (WT) rats. While Vdr-R270L\/H301Q rats exhibited normal skin formation similar to WT rats, Vdr-KO rats showed remarkable hyperkeratosis and trans-epidermal water loss in the skin. RNA sequencing and proteomic analysis revealed that the gene and protein expression patterns in Vdr-KO rats significantly differed from those in WT and Vdr-R270L\/H301Q rats, with a marked decrease in the expression of factors involved in Shh, Wnt, and Bmp signaling pathways, a dramatic reduction in the expression of hair keratins, and a substantial increase in the expression of epidermal keratins. This study clearly demonstrated that non-liganded VDR is significantly involved in the differentiation, proliferation, and cell death of keratinocytes in hair follicles and the epidermis.<\/jats:p>","DOI":"10.3390\/ijms26010422","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T09:17:02Z","timestamp":1736155022000},"page":"422","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Ligand-Independent Vitamin D Receptor Actions Essential for Keratinocyte Homeostasis in the Skin"],"prefix":"10.3390","volume":"26","author":[{"given":"Satoko","family":"Kise","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, Kanazawa University Hospital, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Ishikawa, Japan"},{"name":"Division of Probe Chemistry for Disease Analysis, Research Center for Experimental Modeling of Human Disease, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8460, Ishikawa, Japan"},{"name":"Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu 939-0398, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Morita","sequence":"additional","affiliation":[{"name":"Division of Evolutionary Developmental Biology, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji, Okazaki 444-8585, Aichi, Japan"},{"name":"Department of Basic Biology, School of Life Science, The Graduate University for Advanced Studies, SOKENDAI, Hayama, Miura 240-0115, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7064-8185","authenticated-orcid":false,"given":"Toshiyuki","family":"Sakaki","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu 939-0398, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Kimura","sequence":"additional","affiliation":[{"name":"Division of Probe Chemistry for Disease Analysis, Research Center for Experimental Modeling of Human Disease, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8460, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seigo","family":"Kinuya","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Kanazawa University Hospital, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu 939-0398, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1210\/er.2008-0004","article-title":"Vitamin D and human health: Lessons from vitamin D receptor null mice","volume":"29","author":"Bouillon","year":"2008","journal-title":"Endocr. 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