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Augmented Pla2g4c/Ptgs2/Hpgds axis in bronchial smooth muscle tissues of experimental asthma.

ABSTRACT: 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 PLA2 group 4c (Pla2g4c)/COX-2 (Ptgs2)/PGD2 synthase 2 (Hpgds) axis. PGD2 level in bronchoalveolar fluids of the OA-challenged mice was significantly increased. A 24-h incubation of BSM tissues with PGD2 caused a hyperresponsiveness to ACh in naive control mice. CONCLUSIONS:AA metabolism is shifted towards PGD2 production in BSM tissues of asthma. Increased PGD2 level in the airways might be a cause of the BSM hyperresponsiveness in asthma.

SUBMITTER: Chiba Y

PROVIDER: S-EPMC6116991 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Augmented Pla2g4c/Ptgs2/Hpgds axis in bronchial smooth muscle tissues of experimental asthma.

Chiba Yoshihiko Y Suto Wataru W Sakai Hiroyasu H

PloS one 20180830 8

<h4>Rationale</h4>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.<h4>Objectives</h4>To identify differentially expressed genes (DEGs) related to the bronchial smooth muscle (BSM) hyper-contractility in a murine asthma model.<h4>Methods</h4>The ovalbumin (OA)-sensitized mice were repeatedly challenged with aerosolized OA to i ...[more]

PMID: 30161143

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Project description:BackgroundThe effectiveness of bronchial thermoplasty (BT) has been reported in patients with severe asthma. This study compared the effects of BT and cryoballoon ablation (CBA) therapy on the airway smooth muscle (ASM).MethodsEight healthy male beagle dogs were included in this experiment. In the preliminary experiment, one dog received BT treatment for both lower lobe bronchus, another dog received CBA treatment for 7 s on the upper and lower lobe of right bronchus, and 30 s on the left upper and lower lobe. The treatments were performed twice at an interval of 1 month. In subsequent experiments, the right lower lobe bronchus was treated with BT, and the left lower lobe bronchus was treated with CBA. The effects of treatment were observed after 1 (n = 3) month and 6 months (n = 3). Hematoxylin-eosin staining, Masson trichrome staining, and immunohistochemical staining were used to compare the effects of BT and CBA therapy on the ASM thickness, collagen fibers synthesis, and M3 receptor expression after treatment. One-way analysis of variance with Dunnett post hoc test was used to analyze the differences among groups.ResultsIn the preliminary experiment, the ASM ablation effect of 30-s CBA was equivalent to that of 7-s CBA (ASM thickness: 30.52 ± 7.75 μm vs. 17.57 ± 15.20 μm, P = 0.128), but the bronchial mucociliary epithelium did not recover, and large numbers of inflammatory cells had infiltrated the mucosal epithelium at 1-month post-CBA with 30-s freezing. Therefore, we chose 7 s as the CBA treatment time in our follow-up experiments. Compared with the control group (35.81 ± 11.02 μm), BT group and CBA group (13.41 ± 4.40 μm and 4.81 ± 4.44 μm, respectively) had significantly decreased ASM thickness after 1 month (P < 0.001). Furthermore, the ASM thickness was significantly lower in the 1-month post-CBA group than in the 1-month post-BT group (P = 0.015). There was no significant difference in ASM thickness between the BT and CBA groups after six months (9.92 ± 4.42 μm vs. 7.41 ± 7.20 μm, P = 0.540). Compared with the control group (0.161 ± 0.013), the average optical density of the ASM M3 receptor was significantly decreased in 6-month post-BT, 1-month post-CBA, and 6-month post-CBA groups (0.070 ± 0.022, 0.072 ± 0.012, 0.074 ± 0.008, respectively; all P < 0.001). There was no significant difference in the average optical density of ASM M3 receptor between the BT and CBA therapy groups after six months (P = 0.613).ConclusionsCBA therapy effectively ablates the ASM, and its ablation effect is equivalent to that of BT with a shorter onset time. A neural mechanism is involved in both BT and CBA therapy.

Dataset Information

Augmented Pla2g4c/Ptgs2/Hpgds axis in bronchial smooth muscle tissues of experimental asthma.

Publications

Augmented Pla2g4c/Ptgs2/Hpgds axis in bronchial smooth muscle tissues of experimental asthma.

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