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Effect of Intrauterine Smoke Exposure on microRNA-15a Expression in Human Lung Development and Subsequent Asthma Risk

Background: In utero smoke (IUS) exposure is associated with asthma susceptibility. Objective: We sought to test the hypothesis that changes in miRNA expression by IUS exposure during human lung development is associated with asthma susceptibility. Methods: Gene expression was profiled from 53 IUS u...

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Autores principales: Sharma, Sunita, Kho, Alvin T., Chhabra, Divya, Haley, Kathleen, Vyhlidal, Carrie, Gaedigk, Roger, Leeder, J. Steven, Tantisira, Kelan G., Raby, Benjamin, Weiss, Scott T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761806/
https://www.ncbi.nlm.nih.gov/pubmed/33291534
http://dx.doi.org/10.3390/healthcare8040536
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author Sharma, Sunita
Kho, Alvin T.
Chhabra, Divya
Haley, Kathleen
Vyhlidal, Carrie
Gaedigk, Roger
Leeder, J. Steven
Tantisira, Kelan G.
Raby, Benjamin
Weiss, Scott T.
author_facet Sharma, Sunita
Kho, Alvin T.
Chhabra, Divya
Haley, Kathleen
Vyhlidal, Carrie
Gaedigk, Roger
Leeder, J. Steven
Tantisira, Kelan G.
Raby, Benjamin
Weiss, Scott T.
author_sort Sharma, Sunita
collection PubMed
description Background: In utero smoke (IUS) exposure is associated with asthma susceptibility. Objective: We sought to test the hypothesis that changes in miRNA expression by IUS exposure during human lung development is associated with asthma susceptibility. Methods: Gene expression was profiled from 53 IUS unexposed and 51 IUS exposed human fetal lung tissues. We tested for the differential expression of miRNAs across post-conception age and by IUS using linear models with covariate adjustment. We tested the IUS-associated miRNAs for association with their gene expression targets using pair-wise inverse correlation. Using our mouse model, we investigated the persistence of the IUS-associated miRNA signature using RT-PCR from the lungs of mouse pups with and without IUS at postnatal day 14. MiRNAs were then tested for association with asthma and exacerbations using whole blood gene expression profiles from Asthma BRIDGE. Results: Five miRNAs were differentially expressed across post-conception age (adjusted p < 0.0002) including two that were differentially expressed by IUS exposure in human fetal lung (p < 0.05). MiR-15a was differentially expressed by post-conception age (p = 0.00002), IUS exposure in human fetal lung (p = 0.005), and in the post-natal mouse lung (p = 0.01). MiR-15a was also associated with the in utero expression of GSDMB (adjusted p = 0.0002), a known childhood asthma gene and with asthma exacerbations (p = 0.0009) in Asthma BRIDGE. Thus, miR-15a is expressed during human lung development, is impacted by IUS exposure, regulates the intrauterine expression of asthma genes, and is associated with asthma severity. Conclusions: These results provide evidence for the role of miR-15a in the fetal origin of asthma.
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spelling pubmed-77618062020-12-26 Effect of Intrauterine Smoke Exposure on microRNA-15a Expression in Human Lung Development and Subsequent Asthma Risk Sharma, Sunita Kho, Alvin T. Chhabra, Divya Haley, Kathleen Vyhlidal, Carrie Gaedigk, Roger Leeder, J. Steven Tantisira, Kelan G. Raby, Benjamin Weiss, Scott T. Healthcare (Basel) Article Background: In utero smoke (IUS) exposure is associated with asthma susceptibility. Objective: We sought to test the hypothesis that changes in miRNA expression by IUS exposure during human lung development is associated with asthma susceptibility. Methods: Gene expression was profiled from 53 IUS unexposed and 51 IUS exposed human fetal lung tissues. We tested for the differential expression of miRNAs across post-conception age and by IUS using linear models with covariate adjustment. We tested the IUS-associated miRNAs for association with their gene expression targets using pair-wise inverse correlation. Using our mouse model, we investigated the persistence of the IUS-associated miRNA signature using RT-PCR from the lungs of mouse pups with and without IUS at postnatal day 14. MiRNAs were then tested for association with asthma and exacerbations using whole blood gene expression profiles from Asthma BRIDGE. Results: Five miRNAs were differentially expressed across post-conception age (adjusted p < 0.0002) including two that were differentially expressed by IUS exposure in human fetal lung (p < 0.05). MiR-15a was differentially expressed by post-conception age (p = 0.00002), IUS exposure in human fetal lung (p = 0.005), and in the post-natal mouse lung (p = 0.01). MiR-15a was also associated with the in utero expression of GSDMB (adjusted p = 0.0002), a known childhood asthma gene and with asthma exacerbations (p = 0.0009) in Asthma BRIDGE. Thus, miR-15a is expressed during human lung development, is impacted by IUS exposure, regulates the intrauterine expression of asthma genes, and is associated with asthma severity. Conclusions: These results provide evidence for the role of miR-15a in the fetal origin of asthma. MDPI 2020-12-04 /pmc/articles/PMC7761806/ /pubmed/33291534 http://dx.doi.org/10.3390/healthcare8040536 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sharma, Sunita
Kho, Alvin T.
Chhabra, Divya
Haley, Kathleen
Vyhlidal, Carrie
Gaedigk, Roger
Leeder, J. Steven
Tantisira, Kelan G.
Raby, Benjamin
Weiss, Scott T.
Effect of Intrauterine Smoke Exposure on microRNA-15a Expression in Human Lung Development and Subsequent Asthma Risk
title Effect of Intrauterine Smoke Exposure on microRNA-15a Expression in Human Lung Development and Subsequent Asthma Risk
title_full Effect of Intrauterine Smoke Exposure on microRNA-15a Expression in Human Lung Development and Subsequent Asthma Risk
title_fullStr Effect of Intrauterine Smoke Exposure on microRNA-15a Expression in Human Lung Development and Subsequent Asthma Risk
title_full_unstemmed Effect of Intrauterine Smoke Exposure on microRNA-15a Expression in Human Lung Development and Subsequent Asthma Risk
title_short Effect of Intrauterine Smoke Exposure on microRNA-15a Expression in Human Lung Development and Subsequent Asthma Risk
title_sort effect of intrauterine smoke exposure on microrna-15a expression in human lung development and subsequent asthma risk
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761806/
https://www.ncbi.nlm.nih.gov/pubmed/33291534
http://dx.doi.org/10.3390/healthcare8040536
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