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2017 ; 72
(1
): 74-82
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Latrophilin receptors: novel bronchodilator targets in asthma
#MMPMID27325752
Faiz A
; Donovan C
; Nieuwenhuis MA
; van den Berge M
; Postma DS
; Yao S
; Park CY
; Hirsch R
; Fredberg JJ
; Tjin G
; Halayko AJ
; Rempel KL
; Ward JP
; Lee T
; Bossé Y
; Nickle DC
; Obeidat M
; Vonk JM
; Black JL
; Oliver BG
; Krishnan R
; McParland B
; Bourke JE
; Burgess JK
Thorax
2017[Jan]; 72
(1
): 74-82
PMID27325752
show ga
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.