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All-Trans Retinoic Acid Modulates ORMDL3 Expression via Transcriptional Regulation

All-trans retinoic acid (ATRA) is an active metabolite of Vitamin A, it shows protective effects on asthma, including maintains airway epithelial integrity, inhibits asthma effector cells differentiation, modulates immune response, et al. However, the promoting effect of ATRA on Th2 response has res...

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Autores principales: Zhuang, Li-Li, Huang, Bo-Xian, Feng, Jie, Zhu, Liang-Hua, Jin, Rui, Qiu, Ling-Zhi, Zhou, Guo-Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812219/
https://www.ncbi.nlm.nih.gov/pubmed/24204796
http://dx.doi.org/10.1371/journal.pone.0077304
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author Zhuang, Li-Li
Huang, Bo-Xian
Feng, Jie
Zhu, Liang-Hua
Jin, Rui
Qiu, Ling-Zhi
Zhou, Guo-Ping
author_facet Zhuang, Li-Li
Huang, Bo-Xian
Feng, Jie
Zhu, Liang-Hua
Jin, Rui
Qiu, Ling-Zhi
Zhou, Guo-Ping
author_sort Zhuang, Li-Li
collection PubMed
description All-trans retinoic acid (ATRA) is an active metabolite of Vitamin A, it shows protective effects on asthma, including maintains airway epithelial integrity, inhibits asthma effector cells differentiation, modulates immune response, et al. However, the promoting effect of ATRA on Th2 response has restricted the clinical application of ATRA in asthma treatment. ORMDL3 is a candidate gene of childhood onset asthma, and high-transcript of ORMDL3 is associated with the development of asthma. Here we show that ATRA increases ORMDL3 production in vitro via inducing PKA-dependent CREB phosphorylation which in turn binds to the CRE element in promoter region of ORMDL3 and initiates ORMDL3 transcription. This finding is in consistent with the previous reports that ATRA could regulate target genes without the presence of retinoic acid response element (RARE) in promoter region but through other signals such as PKA/CREB. Nevertheless, in the present study, the traditional signal pathway of ATRA, retinoic acid receptor (RAR) signal transduction pathway, indirectly modulated ORMDL3 expression. RAR-α agonist (Am-80) increased ORMDL3 production even though there was no RARE in ORMDL3 promoter, introns or 3′-downstream region. Besides, the signal of RAR might differ from that of ATRA since Am-80 failed to induce CREB activation. In conclusion, our data indicate that ATRA facilitates ORMDL3 production probable through PKA/CREB, and this may be a starting point for more detailed mechanism researches on ATRA and asthma.
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spelling pubmed-38122192013-11-07 All-Trans Retinoic Acid Modulates ORMDL3 Expression via Transcriptional Regulation Zhuang, Li-Li Huang, Bo-Xian Feng, Jie Zhu, Liang-Hua Jin, Rui Qiu, Ling-Zhi Zhou, Guo-Ping PLoS One Research Article All-trans retinoic acid (ATRA) is an active metabolite of Vitamin A, it shows protective effects on asthma, including maintains airway epithelial integrity, inhibits asthma effector cells differentiation, modulates immune response, et al. However, the promoting effect of ATRA on Th2 response has restricted the clinical application of ATRA in asthma treatment. ORMDL3 is a candidate gene of childhood onset asthma, and high-transcript of ORMDL3 is associated with the development of asthma. Here we show that ATRA increases ORMDL3 production in vitro via inducing PKA-dependent CREB phosphorylation which in turn binds to the CRE element in promoter region of ORMDL3 and initiates ORMDL3 transcription. This finding is in consistent with the previous reports that ATRA could regulate target genes without the presence of retinoic acid response element (RARE) in promoter region but through other signals such as PKA/CREB. Nevertheless, in the present study, the traditional signal pathway of ATRA, retinoic acid receptor (RAR) signal transduction pathway, indirectly modulated ORMDL3 expression. RAR-α agonist (Am-80) increased ORMDL3 production even though there was no RARE in ORMDL3 promoter, introns or 3′-downstream region. Besides, the signal of RAR might differ from that of ATRA since Am-80 failed to induce CREB activation. In conclusion, our data indicate that ATRA facilitates ORMDL3 production probable through PKA/CREB, and this may be a starting point for more detailed mechanism researches on ATRA and asthma. Public Library of Science 2013-10-29 /pmc/articles/PMC3812219/ /pubmed/24204796 http://dx.doi.org/10.1371/journal.pone.0077304 Text en © 2013 Zhuang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zhuang, Li-Li
Huang, Bo-Xian
Feng, Jie
Zhu, Liang-Hua
Jin, Rui
Qiu, Ling-Zhi
Zhou, Guo-Ping
All-Trans Retinoic Acid Modulates ORMDL3 Expression via Transcriptional Regulation
title All-Trans Retinoic Acid Modulates ORMDL3 Expression via Transcriptional Regulation
title_full All-Trans Retinoic Acid Modulates ORMDL3 Expression via Transcriptional Regulation
title_fullStr All-Trans Retinoic Acid Modulates ORMDL3 Expression via Transcriptional Regulation
title_full_unstemmed All-Trans Retinoic Acid Modulates ORMDL3 Expression via Transcriptional Regulation
title_short All-Trans Retinoic Acid Modulates ORMDL3 Expression via Transcriptional Regulation
title_sort all-trans retinoic acid modulates ormdl3 expression via transcriptional regulation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812219/
https://www.ncbi.nlm.nih.gov/pubmed/24204796
http://dx.doi.org/10.1371/journal.pone.0077304
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