{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T05:22:25Z","timestamp":1783574545161,"version":"3.55.0"},"reference-count":37,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,4,5]],"date-time":"2019-04-05T00:00:00Z","timestamp":1554422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2011\/12696-4; 2014\/03561-6"],"award-info":[{"award-number":["2011\/12696-4; 2014\/03561-6"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The vitamin D receptor (VDR) mediates vitamin D actions beyond bone health. While VDR activation by 1,25-dihydroxyvitamin D (1,25D) leads to robust transcriptional regulation, less is known about VDR actions in the absence of 1,25D. We analyzed the transcriptomic response to 1,25D in fibroblasts bearing a severe homozygous hereditary vitamin D resistant rickets-related p.Arg30* VDR mutation (MUT) and in control fibroblasts (CO). Roughly 4.5% of the transcriptome was regulated by 1,25D in CO fibroblasts, while MUT cells without a functional VDR were insensitive to 1,25D. Novel VDR target genes identified in human fibroblasts included bone and cartilage factors CILP, EFNB2, and GALNT12. Vehicle-treated CO and MUT fibroblasts had strikingly different transcriptomes, suggesting basal VDR activity. Indeed, oppositional transcriptional effects in basal conditions versus after 1,25D activation were implied for a subset of target genes mostly involved with cell cycle. Cell proliferation assays corroborated this conjectured oppositional basal VDR activity, indicating that precise 1,25D dosage in target tissues might be essential for modulating vitamin D actions in human health.<\/jats:p>","DOI":"10.3390\/cells8040318","type":"journal-article","created":{"date-parts":[[2019,4,5]],"date-time":"2019-04-05T11:36:01Z","timestamp":1554464161000},"page":"318","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Transcriptomic Response to 1,25-Dihydroxyvitamin D in Human Fibroblasts with or without a Functional Vitamin D Receptor (VDR): Novel Target Genes and Insights into VDR Basal Transcriptional Activity"],"prefix":"10.3390","volume":"8","author":[{"given":"Pedro L. F.","family":"Costa","sequence":"first","affiliation":[{"name":"Laboratorio de Endocrinologia Celular e Molecular LIM-25 e Unidade de Doencas Osteometabolicas, Divisao de Endocrinologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP 01246-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica M.","family":"Fran\u00e7a","sequence":"additional","affiliation":[{"name":"Laboratorio de Endocrinologia Celular e Molecular LIM-25 e Unidade de Doencas Osteometabolicas, Divisao de Endocrinologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP 01246-903, Brazil"},{"name":"Laboratorio de Hormonios e Genetica Molecular LIM-42, Divisao de Endocrinologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP 05403-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria L.","family":"Katayama","sequence":"additional","affiliation":[{"name":"Departamento de Radiologia e Oncologia, Instituto do Cancer do Estado de Sao Paulo (ICESP), Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo T.","family":"Carneiro","sequence":"additional","affiliation":[{"name":"Laboratorio de Endocrinologia Celular e Molecular LIM-25 e Unidade de Doencas Osteometabolicas, Divisao de Endocrinologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP 01246-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina M.","family":"Martin","sequence":"additional","affiliation":[{"name":"Laboratorio de Hormonios e Genetica Molecular LIM-42, Divisao de Endocrinologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP 05403-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A. K.","family":"Folgueira","sequence":"additional","affiliation":[{"name":"Departamento de Radiologia e Oncologia, Instituto do Cancer do Estado de Sao Paulo (ICESP), Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C.","family":"Latronico","sequence":"additional","affiliation":[{"name":"Laboratorio de Hormonios e Genetica Molecular LIM-42, Divisao de Endocrinologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP 05403-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4863-2544","authenticated-orcid":false,"given":"Bruno","family":"Ferraz-de-Souza","sequence":"additional","affiliation":[{"name":"Laboratorio de Endocrinologia Celular e Molecular LIM-25 e Unidade de Doencas Osteometabolicas, Divisao de Endocrinologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP 01246-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,5]]},"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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