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Effects of MicroRNA-21 on Endothelial-to-mesenchymal Transition and Its Role in the Pathogenesis of Chronic Obstructive Pulmonary Disease

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Abstract

Objectives: Chronic obstructive pulmonary disease (COPD) is a disease characterized by persistent airflow restriction. This study aims to explore whether there is endothelial-to-mesenchymal transition (EndMT) in COPD mice and to explore the relationship between microRNA-21 (miR-21) and EndMT.

Methods: We established the COPD and the gene knockout COPD animal model (both cigarette smoke-induced). Mice were divided into 3 groups (=4): a control group, a COPD group, and a knockout COPD (miR-21/-COPD) group. Masson trichrome staining was used to observe the deposition of collagen around the perivascular. The relative protein levels and positions of endothelial cell markers including vascular endothelial-cadherin (VE-cadherin), endothelial nitric oxide synthase (eNOS), and platelet endothelial cell adhesion molecule-1 (CD31) as well as mesenchymal cell markers including α-smooth muscle actin (α-SMA) and neural cadherin (N-cadherin) in lung tissues were observed by immunohistochemical staining.

Results: Compared with the control group, the area of collagen fibril deposition was increased in the COPD group (<0.05), the expression levels of VE-cadherin, eNOS, and CD31 were all decreased (all <0.05), and the expression levels of α-SMA and N-cadherin were increased (both <0.05). Compared with the COPD group, the miR-21/-COPD group had a reduced area of collagen fiber deposition (<0.05), the expression levels of VE-cadherin, eNOS, and CD31 were all increased (all <0.05), and the expression levels of α-SMA and N-cadherin were decreased (both <0.05).

Conclusions: There is a EndMT process in cigarette smoke-induced COPD animal models. gene knockdown could reduce collagen deposition area and inhibit the EndMT process in COPD mice.

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