Gene Expression Profiles in Human and Mouse Primary Cells Provide New Insights into the Differential Actions of Vitamin D-3 Metabolites
Tuohimaa, Pentti ; Wang, Jing-Huan ; Khan, Sofia ; Kuuslahti, Marianne ; Qian, Kui ; Manninen, Tommi ; Auvinen, Petri ; Vihinen, Mauno LU
and Lou, Yan-Ru
(2013)
In PLoS ONE
8(10).
- Abstract
- 1 alpha,25-Dihydroxyvitamin D-3 (1 alpha,25(OH)(2)D-3) had earlier been regarded as the only active hormone. The newly identified actions of 25-hydroxyvitamin D-3 (25(OH)D-3) and 24R,25-dihydroxyvitamin D-3 (24R,25(OH)(2)D-3) broadened the vitamin D-3 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)D-3 into 1 alpha,25(OH)(2)D-3 by 1 alpha-hydroxylase (encoded by... (More)
- 1 alpha,25-Dihydroxyvitamin D-3 (1 alpha,25(OH)(2)D-3) had earlier been regarded as the only active hormone. The newly identified actions of 25-hydroxyvitamin D-3 (25(OH)D-3) and 24R,25-dihydroxyvitamin D-3 (24R,25(OH)(2)D-3) broadened the vitamin D-3 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)D-3 into 1 alpha,25(OH)(2)D-3 by 1 alpha-hydroxylase (encoded by the gene CYP27B1), displayed regulation of 164, 171, and 175 genes by treatment with 1 alpha,25(OH)(2)D-3, 25(OH)D-3, and 24R,25(OH)(2)D-3, respectively. Mouse primary Cyp27b1 knockout fibroblasts (mCyp27b1(-/-)), which lack 1 alpha-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 1 alpha,25(OH)(2)D-3 and 25(OH)D-3 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 D-3 hormones with clearly different biological activities. This study presents a new conceptual insight into the vitamin D-3 endocrine system, which may guide the strategic use of vitamin D-3 in disease prevention and treatment. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4163382
- author
- Tuohimaa, Pentti
; Wang, Jing-Huan
; Khan, Sofia
; Kuuslahti, Marianne
; Qian, Kui
; Manninen, Tommi
; Auvinen, Petri
; Vihinen, Mauno
LU
and Lou, Yan-Ru
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 8
- issue
- 10
- article number
- e75338
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000325552200017
- scopus:84885158019
- pmid:24116037
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0075338
- language
- English
- LU publication?
- yes
- id
- 1508deea-e59c-4edc-bd8f-02d30df1b9b6 (old id 4163382)
- date added to LUP
- 2016-04-01 14:35:15
- date last changed
- 2022-01-28 01:24:56
@article{1508deea-e59c-4edc-bd8f-02d30df1b9b6,
abstract = {{1 alpha,25-Dihydroxyvitamin D-3 (1 alpha,25(OH)(2)D-3) had earlier been regarded as the only active hormone. The newly identified actions of 25-hydroxyvitamin D-3 (25(OH)D-3) and 24R,25-dihydroxyvitamin D-3 (24R,25(OH)(2)D-3) broadened the vitamin D-3 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)D-3 into 1 alpha,25(OH)(2)D-3 by 1 alpha-hydroxylase (encoded by the gene CYP27B1), displayed regulation of 164, 171, and 175 genes by treatment with 1 alpha,25(OH)(2)D-3, 25(OH)D-3, and 24R,25(OH)(2)D-3, respectively. Mouse primary Cyp27b1 knockout fibroblasts (mCyp27b1(-/-)), which lack 1 alpha-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 1 alpha,25(OH)(2)D-3 and 25(OH)D-3 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 D-3 hormones with clearly different biological activities. This study presents a new conceptual insight into the vitamin D-3 endocrine system, which may guide the strategic use of vitamin D-3 in disease prevention and treatment.}},
author = {{Tuohimaa, Pentti and Wang, Jing-Huan and Khan, Sofia and Kuuslahti, Marianne and Qian, Kui and Manninen, Tommi and Auvinen, Petri and Vihinen, Mauno and Lou, Yan-Ru}},
issn = {{1932-6203}},
language = {{eng}},
number = {{10}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{Gene Expression Profiles in Human and Mouse Primary Cells Provide New Insights into the Differential Actions of Vitamin D-3 Metabolites}},
url = {{https://lup.lub.lu.se/search/files/4057134/4609870.pdf}},
doi = {{10.1371/journal.pone.0075338}},
volume = {{8}},
year = {{2013}},
}