{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:29:39Z","timestamp":1787495379082,"version":"build-2736575974"},"reference-count":101,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:00:00Z","timestamp":1760140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH National Eye Institute","award":["R01EY021747"],"award-info":[{"award-number":["R01EY021747"]}]},{"name":"NIH National Eye Institute","award":["P30 EY031631"],"award-info":[{"award-number":["P30 EY031631"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Corneal fibrosis, a significant source of visual impairment, can result from keratocyte-to-myofibroblast transdifferentiation during wound healing. This study investigated the antifibrotic role of 1,25-dihydroxyvitamin D3 (1,25 Vit D) and the lesser-known vitamin D, 24,25-dihydroxyvitamin D3 (24,25 Vit D), in human and mouse corneal stromal cells (HSCs and MSCs) and in a Vit D receptor knockout (VDR KO) mouse model. Cells were treated with TGF-\u03b21 \u00b1 Vit D metabolites and the expression of fibrotic and antifibrotic genes and proteins was evaluated. Both metabolites significantly reduced \u03b1-smooth muscle actin levels in HSCs, MSCs and organ-cultured mouse corneas (p &lt; 0.05). They also upregulated the mRNA expression of BMP2, BMP6, BMPR2, and TGF-\u03b23, as well as the protein expression of BMP6 and TGF-\u03b23. VDR KO corneas subjected to alkali injury exhibited increased fibrotic responses and reduced CD45+ immune cell infiltration compared to wild-type controls. Notably, 24,25 Vit D exerted antifibrotic effects even in VDR KO cells, and the alternative 24,25 Vit D receptor FAM57B was expressed in all corneal cell layers. These results reveal consistent antifibrotic effects of both 1,25 and 24,25 Vit D across species, support the existence of VDR-independent mechanisms in the cornea, and offer new insights into potential therapeutic strategies for preventing corneal fibrosis.<\/jats:p>","DOI":"10.3390\/cells14201583","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:13:27Z","timestamp":1760361207000},"page":"1583","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Suppression of Cornea Stromal Fibrosis by Vitamin D"],"prefix":"10.3390","volume":"14","author":[{"given":"Xiaowen","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2079-9887","authenticated-orcid":false,"given":"Mitchell A.","family":"Watsky","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,11]]},"reference":[{"key":"ref_1","first-page":"214","article-title":"Corneal blindness: A global perspective","volume":"79","author":"Whitcher","year":"2001","journal-title":"Bull. 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