Open AccessAugmented Pla2g4c/Ptgs2/Hpgds axis in bronchial smooth muscle tissues of experimental asthma
Author(s) -
Yoshihiko Chiba,
Wataru Suto,
Hiroyasu Sakai
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0202623
Subject(s) - ovalbumin , kegg , transcriptome , contractility , bronchial hyperresponsiveness , asthma , immunology , microarray , chemistry , medicine , biology , endocrinology , gene expression , immune system , biochemistry , gene , lung , respiratory disease
Rationale Augmented smooth muscle contractility of the airways is one of the causes of airway hyperresponsiveness in asthmatics. However, the mechanism of the altered properties of airway smooth muscle cells is not well understood. Objectives To identify differentially expressed genes (DEGs) related to the bronchial smooth muscle (BSM) hyper-contractility in a murine asthma model. Methods The ovalbumin (OA)-sensitized mice were repeatedly challenged with aerosolized OA to induce asthmatic reaction. Transcriptomic profiles were generated by microarray analysis of BSM tissues from the OA-challenged and control animals, and KEGG (Kyoto Encyclopedia of Genes and Genomes) Pathway Analysis was applied. Measurements and main results Tension study showed a BSM hyperresponsiveness to acetylcholine (ACh) in the OA-challenged mice. A total of 770 genes were differentially expressed between the OA-challenged and control animals. Pathway analysis showed a significant change in arachidonic acid (AA) metabolism pathway in BSM tissues of the OA-challenged mice. Validation of DEGs by quantitative RT-PCR showed a significant increase in PLA 2 group 4c ( Pla2g4c )/COX-2 ( Ptgs2 )/PGD 2 synthase 2 ( Hpgds ) axis. PGD 2 level in bronchoalveolar fluids of the OA-challenged mice was significantly increased. A 24-h incubation of BSM tissues with PGD 2 caused a hyperresponsiveness to ACh in naive control mice. Conclusions AA metabolism is shifted towards PGD 2 production in BSM tissues of asthma. Increased PGD 2 level in the airways might be a cause of the BSM hyperresponsiveness in asthma.