Latrophilin receptors: Novel bronchodilator targets in asthma

Faiz, A; Donovan, C; Nieuwenhuis, MAE; Van Den Berge, M; Postma, DS; Yao, S; Park, CY; Hirsch, R; Fredberg, JJ; Tjin, G; Halayko, AJ; Rempel, KL; Ward, JPT; Lee, T; Bossé, Y; Nickle, DC; Obeidat, M; Vonk, JM; Black, JL; Oliver, BG; Krishnan, R; McParland, B; Bourke, JE; Burgess, JK

Latrophilin receptors: Novel bronchodilator targets in asthma

Donovan, C Nieuwenhuis, MAE Van Den Berge, M Postma, DS Yao, S Park, CY Hirsch, R Fredberg, JJ Tjin, G Halayko, AJ Rempel, KL Ward, JPT Lee, T Bossé, Y Nickle, DC Obeidat, M Vonk, JM Black, JL Oliver, BG

Krishnan, R McParland, B Bourke, JE Burgess, JK

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Publication Type:: Journal Article
Citation:: Thorax, 2017, 72 (1), pp. 74 - 82
Issue Date:: 2017-01-01

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Field	Value	Language
dc.contributor.author	Faiz, A https://orcid.org/0000-0003-1740-3538	en_US
dc.contributor.author	Donovan, C	en_US
dc.contributor.author	Nieuwenhuis, MAE	en_US
dc.contributor.author	Van Den Berge, M	en_US
dc.contributor.author	Postma, DS	en_US
dc.contributor.author	Yao, S	en_US
dc.contributor.author	Park, CY	en_US
dc.contributor.author	Hirsch, R	en_US
dc.contributor.author	Fredberg, JJ	en_US
dc.contributor.author	Tjin, G	en_US
dc.contributor.author	Halayko, AJ	en_US
dc.contributor.author	Rempel, KL	en_US
dc.contributor.author	Ward, JPT	en_US
dc.contributor.author	Lee, T	en_US
dc.contributor.author	Bossé, Y	en_US
dc.contributor.author	Nickle, DC	en_US
dc.contributor.author	Obeidat, M	en_US
dc.contributor.author	Vonk, JM	en_US
dc.contributor.author	Black, JL	en_US
dc.contributor.author	Oliver, BG https://orcid.org/0000-0002-7122-9262	en_US
dc.contributor.author	Krishnan, R	en_US
dc.contributor.author	McParland, B	en_US
dc.contributor.author	Bourke, JE	en_US
dc.contributor.author	Burgess, JK	en_US
dc.date.available	2016-05-19	en_US
dc.date.issued	2017-01-01	en_US
dc.identifier.citation	Thorax, 2017, 72 (1), pp. 74 - 82	en_US
dc.identifier.issn	0040-6376	en_US
dc.identifier.uri	http://hdl.handle.net/10453/115194
dc.description.abstract	© 2017 Published by the BMJ Publishing Group Limited. Background Asthma affects 300 million people worldwide. In asthma, the major cause of morbidity and mortality is acute airway narrowing, due to airway smooth muscle (ASM) hypercontraction, associated with airway remodelling. However, little is known about the transcriptional differences between healthy and asthmatic ASM cells. Objectives To investigate the transcriptional differences between asthmatic and healthy airway smooth muscle cells (ASMC) in culture and investigate the identified targets using in vitro and ex vivo techniques. Methods Human asthmatic and healthy ASMC grown in culture were run on Affymetrix-Hugene-1.0-ST microarrays. Identified candidates were confirmed by PCR, and immunohistochemistry. Functional analysis was conducted using in vitro ASMC proliferation, attachment and contraction assays and ex vivo contraction of mouse airways. Results We suggest a novel role for latrophilin (LPHN) receptors, finding increased expression on ASMC from asthmatics, compared with non-asthmatics in vivo and in vitro, suggesting a role in mediating airway function. A single nucleotide polymorphism in LPHN1 was associated with asthma and with increased LPHN1 expression in lung tissue. When activated, LPHNs regulated ASMC adhesion and proliferation in vitro, and promoted contraction of mouse airways and ASMC. Conclusions Given the need for novel inhibitors of airway remodelling and bronchodilators in asthma, the LPHN family may represent promising novel targets for future dual therapeutic intervention.	en_US
dc.relation	http://purl.org/au-research/grants/nhmrc/APP1026880
dc.relation.ispartof	Thorax	en_US
dc.relation.isbasedon	10.1136/thoraxjnl-2015-207236	en_US
dc.subject.classification	Respiratory System	en_US
dc.subject.mesh	Respiratory System	en_US
dc.subject.mesh	Cells, Cultured	en_US
dc.subject.mesh	Myocytes, Smooth Muscle	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred BALB C	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Asthma	en_US
dc.subject.mesh	Acetylcholine	en_US
dc.subject.mesh	Membrane Proteins	en_US
dc.subject.mesh	Receptors, G-Protein-Coupled	en_US
dc.subject.mesh	Receptors, Peptide	en_US
dc.subject.mesh	Spider Venoms	en_US
dc.subject.mesh	Oligonucleotide Array Sequence Analysis	en_US
dc.subject.mesh	Case-Control Studies	en_US
dc.subject.mesh	Cell Adhesion	en_US
dc.subject.mesh	Cell Proliferation	en_US
dc.subject.mesh	Transcription, Genetic	en_US
dc.subject.mesh	Muscle Contraction	en_US
dc.subject.mesh	Polymorphism, Single Nucleotide	en_US
dc.subject.mesh	Male	en_US
dc.title	Latrophilin receptors: Novel bronchodilator targets in asthma	en_US
dc.type	Journal Article
utslib.citation.volume	1	en_US
utslib.citation.volume	72	en_US
utslib.for	1103 Clinical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
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/Strength - CHT - Health Technologies
utslib.copyright.status	open_access
pubs.issue	1	en_US
pubs.publication-status	Published	en_US
pubs.volume	72	en_US

Abstract:

© 2017 Published by the BMJ Publishing Group Limited. Background Asthma affects 300 million people worldwide. In asthma, the major cause of morbidity and mortality is acute airway narrowing, due to airway smooth muscle (ASM) hypercontraction, associated with airway remodelling. However, little is known about the transcriptional differences between healthy and asthmatic ASM cells. Objectives To investigate the transcriptional differences between asthmatic and healthy airway smooth muscle cells (ASMC) in culture and investigate the identified targets using in vitro and ex vivo techniques. Methods Human asthmatic and healthy ASMC grown in culture were run on Affymetrix-Hugene-1.0-ST microarrays. Identified candidates were confirmed by PCR, and immunohistochemistry. Functional analysis was conducted using in vitro ASMC proliferation, attachment and contraction assays and ex vivo contraction of mouse airways. Results We suggest a novel role for latrophilin (LPHN) receptors, finding increased expression on ASMC from asthmatics, compared with non-asthmatics in vivo and in vitro, suggesting a role in mediating airway function. A single nucleotide polymorphism in LPHN1 was associated with asthma and with increased LPHN1 expression in lung tissue. When activated, LPHNs regulated ASMC adhesion and proliferation in vitro, and promoted contraction of mouse airways and ASMC. Conclusions Given the need for novel inhibitors of airway remodelling and bronchodilators in asthma, the LPHN family may represent promising novel targets for future dual therapeutic intervention.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/115194