 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jul 03, 2018 |
| Title |
Augmented Pla2g4c/Ptgs2/Hpgds Axis in Bronchial Tissues of Experimental Asthma |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
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 BSMs 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 BSMs 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 BSMs with PGD2 caused a hyperresponsiveness to ACh in naive control mice. Conclusions: AA metabolism is shifted towards PGD2 production in BSMs of asthma. Increased PGD2 level in the airways might be a cause of the BSM hyperresponsiveness in asthma.
|
| |
|
| Overall design |
A murine model of allergic bronchial asthma was prepared. In brief, male BALB/c mice (8 weeks of age) were actively sensitized by intraperitoneal injections of 8 µg ovalbumin (OA) with 2 mg Imject Alum on Day 0 and Day 5. The sensitized mice were challenged with aerosolized OA-saline solution (5 mg/mL) for 30 min on Days 12, 16 and 20. A control group of mice received the same immunization procedure but inhaled saline aerosol instead of OA challenge. Twenty-four hours after the last OA challenge, mice were sacrificed by exsanguination from abdominal aorta under urethane anesthesia (1.6 g/kg, i.p.) and both the left and right main bronchi were immediately isolated, and then total RNA was extracted using Trizol reagent according to the manufacturer’s protocol. RNA purity and integrity were evaluated by ND-1000 Spectrophotometer (Thermo Fisher Scientific) and Agilent 2100 Bioanalyzer (Agilent Technologies). To identify differentially expressed genes related to the disease, total RNAs of the OA-challenged (N=4) and control animals (N=4) were subjected to microarray analysis (Agilent One-Color Microarray-Based Gene Expression Analysis protocol (v6.5, Agilent Technologies)) and compared.
|
| |
|
| Contributor(s) |
Chiba Y, Suto W, Sakai H |
| Citation(s) |
30161143, 30918168 |
| Submission date |
Jul 02, 2018 |
| Last update date |
Apr 09, 2019 |
| Contact name |
Yoshihiko Chiba |
| E-mail(s) |
chiba@hoshi.ac.jp
|
| Phone |
81-3-5498-5921
|
| Organization name |
Hoshi University School of Pharmacy
|
| Department |
Department of Physiology and Molecular Sciences
|
| Street address |
2-4-41 Ebara, Shinagawa-ku
|
| City |
Tokyo |
| ZIP/Postal code |
142-8501 |
| Country |
Japan |
| |
|
| Platforms (1) |
| GPL21163 |
Agilent-074809 SurePrint G3 Mouse GE v2 8x60K Microarray [Probe Name version] |
|
| Samples (8)
|
|
| Relations |
| BioProject |
PRJNA478859 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE116504_RAW.tar |
36.7 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...