Acute cigarette smoke-induced eQTL affects formyl peptide receptor expression and lung function.

Pouwels, SD; Wiersma, VR; Fokkema, IE; Berg, M; Ten Hacken, NHT; van den Berge, M; Heijink, I; Faiz, A

Acute cigarette smoke-induced eQTL affects formyl peptide receptor expression and lung function.

Pouwels, SD Wiersma, VR Fokkema, IE Berg, M Ten Hacken, NHT van den Berge, M Heijink, I Faiz, A

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Publisher:: Wiley
Publication Type:: Journal Article
Citation:: Respirology (Carlton, Vic.), 2020
Issue Date:: 2020-10-19

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Field	Value	Language
dc.contributor.author	Pouwels, SD
dc.contributor.author	Wiersma, VR
dc.contributor.author	Fokkema, IE
dc.contributor.author	Berg, M
dc.contributor.author	Ten Hacken, NHT
dc.contributor.author	van den Berge, M
dc.contributor.author	Heijink, I
dc.contributor.author	Faiz, A https://orcid.org/0000-0003-1740-3538
dc.date.accessioned	2020-10-30T19:53:27Z
dc.date.available	2020-09-24
dc.date.available	2020-10-30T19:53:27Z
dc.date.issued	2020-10-19
dc.identifier.citation	Respirology (Carlton, Vic.), 2020
dc.identifier.issn	1323-7799
dc.identifier.issn	1440-1843
dc.identifier.uri	http://hdl.handle.net/10453/143624
dc.description.abstract	BACKGROUND AND OBJECTIVE:Cigarette smoking is one of the most prevalent causes of preventable deaths worldwide, leading to chronic diseases, including chronic obstructive pulmonary disease (COPD). Cigarette smoke is known to induce significant transcriptional modifications throughout the respiratory tract. However, it is largely unknown how genetic profiles influence the smoking-related transcriptional changes and how changes in gene expression translate into altered alveolar epithelial repair responses. METHODS:We performed a candidate-based acute cigarette smoke-induced eQTL study, investigating the association between SNP and differential gene expression of FPR family members in bronchial epithelial cells isolated 24 h after smoking and after 48 h without smoking. The effects FPR1 on lung epithelial integrity and repair upon damage in the presence and absence of cigarette smoke were studied in CRISPR-Cas9-generated lung epithelial knockout cells. RESULTS:One significant (FDR < 0.05) inducible eQTL (rs3212855) was identified that induced a >2-fold change in gene expression. The minor allele of rs3212855 was associated with significantly higher gene expression of FPR1, FPR2 and FPR3 upon smoking. Importantly, the minor allele of rs3212855 was also associated with lower lung function. Alveolar epithelial FPR1 knockout cells were protected against CSE-induced reduction in repair capacity upon wounding. CONCLUSION:We identified a novel smoking-related inducible eQTL that is associated with a smoke-induced increase in the expression of FPR1, FPR2 and FPR3, and with lowered lung function. in vitro FPR1 down-regulation protects against smoke-induced reduction in lung epithelial repair.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Wiley
dc.relation.ispartof	Respirology (Carlton, Vic.)
dc.relation.isbasedon	10.1111/resp.13960
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.subject	11 Medical and Health Sciences
dc.subject.classification	Respiratory System
dc.title	Acute cigarette smoke-induced eQTL affects formyl peptide receptor expression and lung function.
dc.type	Journal Article
utslib.location.activity	Australia
utslib.for	11 Medical and Health Sciences
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	closed_access	*
dc.date.updated	2020-10-30T19:53:15Z
pubs.publication-status	Published

Abstract:

BACKGROUND AND OBJECTIVE:Cigarette smoking is one of the most prevalent causes of preventable deaths worldwide, leading to chronic diseases, including chronic obstructive pulmonary disease (COPD). Cigarette smoke is known to induce significant transcriptional modifications throughout the respiratory tract. However, it is largely unknown how genetic profiles influence the smoking-related transcriptional changes and how changes in gene expression translate into altered alveolar epithelial repair responses. METHODS:We performed a candidate-based acute cigarette smoke-induced eQTL study, investigating the association between SNP and differential gene expression of FPR family members in bronchial epithelial cells isolated 24 h after smoking and after 48 h without smoking. The effects FPR1 on lung epithelial integrity and repair upon damage in the presence and absence of cigarette smoke were studied in CRISPR-Cas9-generated lung epithelial knockout cells. RESULTS:One significant (FDR < 0.05) inducible eQTL (rs3212855) was identified that induced a >2-fold change in gene expression. The minor allele of rs3212855 was associated with significantly higher gene expression of FPR1, FPR2 and FPR3 upon smoking. Importantly, the minor allele of rs3212855 was also associated with lower lung function. Alveolar epithelial FPR1 knockout cells were protected against CSE-induced reduction in repair capacity upon wounding. CONCLUSION:We identified a novel smoking-related inducible eQTL that is associated with a smoke-induced increase in the expression of FPR1, FPR2 and FPR3, and with lowered lung function. in vitro FPR1 down-regulation protects against smoke-induced reduction in lung epithelial repair.

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http://hdl.handle.net/10453/143624