AUTHOR=Ding Zhen , Yu Fei , Sun Yan , Jiao Ning , Shi Lina , Wan Jinghong , Liu Qinghua TITLE=ORMDL3 Promotes Angiogenesis in Chronic Asthma Through the ERK1/2/VEGF/MMP-9 Pathway JOURNAL=Frontiers in Pediatrics VOLUME=9 YEAR=2022 URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2021.708555 DOI=10.3389/fped.2021.708555 ISSN=2296-2360 ABSTRACT=Aim

Angiogenesis plays a vital role in airway remodeling in chronic asthma. ORMDL3 has been identified to be closely associated with the development of asthma remodeling. This study was to investigate the mechanism of ORMDL3 in angiogenesis of chronic asthma.

Methods

BALB/c mice were divided into three groups, including an asthmatic group (group A), a budesonide-treated group (group B), and a normal control group (group C). Hematoxylin and eosin and Masson staining were used to evaluate the pathological changes. Angiogenesis in lung tissue was examined by CD31 staining. The changes of ORMDL3, ERK1/2, and angiogenesis-associated MMP-9 and Vascular endothelial growth factor (VEGF) expression were examined. Furthermore, ORMDL3, MMP-9, and VEGF mRNA and protein levels were examined after transfection in BEAS-2B cells with the ORMDL3-overexpressed lentiviral vector.

Results

Compared with the control group, asthmatic mice indicated more severe airway angiogenesis with increased ORMDL3, ERK1/2, MMP-9, and VEGF expression. Budesonide alleviated airway angiogenesis, and CD31 expression was positive with the levels of ORMDL3, MMP-9, and VEGF (P < 0.01). After successful transfection in BEAS-2B cells with the ORMDL3-overexpressing lentiviral vector, VEGF, and MMP-9 expression were activated in vitro (P < 0.01).

Conclusion

In conclusion, our study provides novel evidence that ORMDL3 promotes angiogenesis through upregulating VEGF and MMP-9 in chronic asthma.