Abstract
AimAngiogenesis 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.MethodsBALB/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.ResultsCompared 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).ConclusionIn conclusion, our study provides novel evidence that ORMDL3 promotes angiogenesis through upregulating VEGF and MMP-9 in chronic asthma.
Highlights
Over the past 20 years, asthma has been a major global public health concern, and the incidence rate has doubled with a younger age trend, the estimated prevalence of which is reported in different countries: 10% in the United Kingdom, 4.8% in France, and 4.8% in Germany approximately [1, 2]
There was a positive association between Vascular endothelial growth factor (VEGF) and p-ERK1/2 (r = 0.676, P < 0.01)
As marker CD31 is a characteristic feature of angiogenesis, these data indicate that ORMDL3 may serve a key role in vessel remodeling
Summary
Over the past 20 years, asthma has been a major global public health concern, and the incidence rate has doubled with a younger age trend, the estimated prevalence of which is reported in different countries: 10% in the United Kingdom, 4.8% in France, and 4.8% in Germany approximately [1, 2]. Asthma is a chronic airway inflammation characterized by airway hyperresponsiveness and remodeling. Angiogenesis in the bronchial airway results in more serious chronic inflammation because a well-developed network of blood vessels enables migration of inflammatory cells into the bronchial wall, which results in bronchial airway remodeling. Vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) are the important angiogenesis-promoting cytokines in asthma [6,7,8]. The expressions of these factors are to be explored, and further works are severely needed to figure out the mechanisms of ORMDL3 in chronic asthma angiogenesis
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