Gene expression profiles in human and mouse primary cells provide new insights into the differential actions of vitamin D3 metabolites.

1α,25-Dihydroxyvitamin D3 (1α,25(OH)2D3) had earlier been regarded as the only active hormone. The newly identified actions of 25-hydroxyvitamin D3 (25(OH)D3) and 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) broadened the vitamin D3 endocrine system, however, the current data are fragmented and a syst...

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Autores principales:	Pentti Tuohimaa, Jing-Huan Wang, Sofia Khan, Marianne Kuuslahti, Kui Qian, Tommi Manninen, Petri Auvinen, Mauno Vihinen, Yan-Ru Lou
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b2d268de62594e819e74d23a0bc30cb4
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spelling	oai:doaj.org-article:b2d268de62594e819e74d23a0bc30cb42021-11-18T08:51:57ZGene expression profiles in human and mouse primary cells provide new insights into the differential actions of vitamin D3 metabolites.1932-620310.1371/journal.pone.0075338https://doaj.org/article/b2d268de62594e819e74d23a0bc30cb42013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24116037/pdf/?tool=EBIhttps://doaj.org/toc/1932-62031α,25-Dihydroxyvitamin D3 (1α,25(OH)2D3) had earlier been regarded as the only active hormone. The newly identified actions of 25-hydroxyvitamin D3 (25(OH)D3) and 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) broadened the vitamin D3 endocrine system, however, the current data are fragmented and a systematic understanding is lacking. Here we performed the first systematic study of global gene expression to clarify their similarities and differences. Three metabolites at physiologically comparable levels were utilized to treat human and mouse fibroblasts prior to DNA microarray analyses. Human primary prostate stromal P29SN cells (hP29SN), which convert 25(OH)D3 into 1α,25(OH)2D3 by 1α-hydroxylase (encoded by the gene CYP27B1), displayed regulation of 164, 171, and 175 genes by treatment with 1α,25(OH)2D3, 25(OH)D3, and 24R,25(OH)2D3, respectively. Mouse primary Cyp27b1 knockout fibroblasts (mCyp27b1 (-/-)), which lack 1α-hydroxylation, displayed regulation of 619, 469, and 66 genes using the same respective treatments. The number of shared genes regulated by two metabolites is much lower in hP29SN than in mCyp27b1 (-/-). By using DAVID Functional Annotation Bioinformatics Microarray Analysis tools and Ingenuity Pathways Analysis, we identified the agonistic regulation of calcium homeostasis and bone remodeling between 1α,25(OH)2D3 and 25(OH)D3 and unique non-classical actions of each metabolite in physiological and pathological processes, including cell cycle, keratinocyte differentiation, amyotrophic lateral sclerosis signaling, gene transcription, immunomodulation, epigenetics, cell differentiation, and membrane protein expression. In conclusion, there are three distinct vitamin D3 hormones with clearly different biological activities. This study presents a new conceptual insight into the vitamin D3 endocrine system, which may guide the strategic use of vitamin D3 in disease prevention and treatment.Pentti TuohimaaJing-Huan WangSofia KhanMarianne KuuslahtiKui QianTommi ManninenPetri AuvinenMauno VihinenYan-Ru LouPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 10, p e75338 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pentti Tuohimaa Jing-Huan Wang Sofia Khan Marianne Kuuslahti Kui Qian Tommi Manninen Petri Auvinen Mauno Vihinen Yan-Ru Lou Gene expression profiles in human and mouse primary cells provide new insights into the differential actions of vitamin D3 metabolites.
description	1α,25-Dihydroxyvitamin D3 (1α,25(OH)2D3) had earlier been regarded as the only active hormone. The newly identified actions of 25-hydroxyvitamin D3 (25(OH)D3) and 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) broadened the vitamin D3 endocrine system, however, the current data are fragmented and a systematic understanding is lacking. Here we performed the first systematic study of global gene expression to clarify their similarities and differences. Three metabolites at physiologically comparable levels were utilized to treat human and mouse fibroblasts prior to DNA microarray analyses. Human primary prostate stromal P29SN cells (hP29SN), which convert 25(OH)D3 into 1α,25(OH)2D3 by 1α-hydroxylase (encoded by the gene CYP27B1), displayed regulation of 164, 171, and 175 genes by treatment with 1α,25(OH)2D3, 25(OH)D3, and 24R,25(OH)2D3, respectively. Mouse primary Cyp27b1 knockout fibroblasts (mCyp27b1 (-/-)), which lack 1α-hydroxylation, displayed regulation of 619, 469, and 66 genes using the same respective treatments. The number of shared genes regulated by two metabolites is much lower in hP29SN than in mCyp27b1 (-/-). By using DAVID Functional Annotation Bioinformatics Microarray Analysis tools and Ingenuity Pathways Analysis, we identified the agonistic regulation of calcium homeostasis and bone remodeling between 1α,25(OH)2D3 and 25(OH)D3 and unique non-classical actions of each metabolite in physiological and pathological processes, including cell cycle, keratinocyte differentiation, amyotrophic lateral sclerosis signaling, gene transcription, immunomodulation, epigenetics, cell differentiation, and membrane protein expression. In conclusion, there are three distinct vitamin D3 hormones with clearly different biological activities. This study presents a new conceptual insight into the vitamin D3 endocrine system, which may guide the strategic use of vitamin D3 in disease prevention and treatment.
format	article
author	Pentti Tuohimaa Jing-Huan Wang Sofia Khan Marianne Kuuslahti Kui Qian Tommi Manninen Petri Auvinen Mauno Vihinen Yan-Ru Lou
author_facet	Pentti Tuohimaa Jing-Huan Wang Sofia Khan Marianne Kuuslahti Kui Qian Tommi Manninen Petri Auvinen Mauno Vihinen Yan-Ru Lou
author_sort	Pentti Tuohimaa
title	Gene expression profiles in human and mouse primary cells provide new insights into the differential actions of vitamin D3 metabolites.
title_short	Gene expression profiles in human and mouse primary cells provide new insights into the differential actions of vitamin D3 metabolites.
title_full	Gene expression profiles in human and mouse primary cells provide new insights into the differential actions of vitamin D3 metabolites.
title_fullStr	Gene expression profiles in human and mouse primary cells provide new insights into the differential actions of vitamin D3 metabolites.
title_full_unstemmed	Gene expression profiles in human and mouse primary cells provide new insights into the differential actions of vitamin D3 metabolites.
title_sort	gene expression profiles in human and mouse primary cells provide new insights into the differential actions of vitamin d3 metabolites.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/b2d268de62594e819e74d23a0bc30cb4
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Gene expression profiles in human and mouse primary cells provide new insights into the differential actions of vitamin D3 metabolites.

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