A Novel Murine Chronic Obstructive Pulmonary Disease Model and the Pathogenic Role of MicroRNA-21

Abstract

Chronic obstructive pulmonary disease (COPD) is a multi-pathogenesis chronic lung disease. The mechanisms underlying COPD have not been adequately illustrated. Many reseachers argue that microRNAs (miRs) could play a crucial role in COPD. The classic animal model of COPD is both time consuming and costly. This study proposes a novel mice COPD model and explores the role of miR-21 in COPD. A total of 50 wide-type (WT) C57BL/6 mice were separated into five euqlly-sized groups—(1) control group (CG), (2) the novel combined method group (NCM, cigarette smoke (CS) exposure for 28 days combined with cigarette smoke extract (CSE) intraperitoneal injection), (3) the short-term CS exposure group (SCSE, CS exposure for 28 days), (4) the CSE intraperitoneal injection group (CSEII, 28 days CSE intraperitoneal injection), and (5) the long-term CS exposure group (LCSE, CS exposure).The body weight gain of mice were recorded and lung function tested once the modeling was done. The pathological changes and the inflammation level by hematoxylin eosin (H&E) staining and immunohistochemical staining (IHS) on the lung tissue sections were also evaluated. The level of miR-21 in the mice lungs of the mice across all groups was detected by RT-qPCR and the effects of miR-21 knock-down in modeled mice were observed. The mice in LCSE and NCM exhibited the most severe inflammation levels and pathological and pathophysiological changes; while the changes for the mice in SCSE and CSEII were less, they remained more severe than the mice in the CG. The level of miR-21 was found to be negatively correlated with lung functions. Moreover, knocking miR-21 down from the modeled mice, ameliorated all those tested COPD-related changes. Our novel modeling method detected virtually the same changes as those detected in the classic method in WT mice, but in less time and cost. Further, it was determined that the level of miR-21 in the lungs could be an indicator of COPD severity and blocking functions of miR-21 could be a potential treatment for early stage COPD.

Dynamic evolution of emphysema and airway remodeling in two mouse models of COPD

“…In addition, the weight measurement was similar to the results of a study by He et al [16]. The weights of mice in the CS and CS + LPS groups were significantly lower than mice in the control group, consistent with the body weight loss of patients with COPD.…”

“…The slides were examined under a light microscope at a photograph documentation facility (Olympus BX53 8l48101, Tokyo, Japan) and the pictures were captured by CellSens Standard. The size of the alveolar space was examined by measuring the mean interalveolar septal wall distance (MLI) using Image-Pro Plus 6.0 software, as previously described [ 16 ]. Briefly, the MLI was measured by dividing the length of diagonals of 10 random fields of each lung tissue by the sum of intercepts counted within diagonals at 100 × magnification (the bronchial regions were not included).…”

MicroRNAs as Potential Regulators of Immune Response Networks in Asthma and Chronic Obstructive Pulmonary Disease

“…Interestingly, downregulation of miR-21 in mice prevented remodeling by CSE ( 113 ). This miRNA is also implicated in the autophagy and apoptosis produced by CSE in lung tissues of both mice and 16HBE cells, being associated with worse lung function, proving its potential as therapeutic target in COPD ( 115 , 116 ).…”

The impacts of anti-inflammatory phosphodiesterase inhibitors on a murine model of chronic pulmonary inflammation

“…The murine model of CS-induced pulmonary emphysema has many similarities to human COPD, including growth delay (Chen, Hansen, Jones, Vlahos, Anderson & Morris, 2008;He, Li, Sun, Zeng, Lu & Xie, 2018), hyper-inflammatory responses and enhanced oxidative stress (Kameyama et al, 2018;Sasaki et al, 2015). By using the C57BL/6 mice strain in this study, we enhanced the susceptibility to CS exposure (Yao et al, 2008).…”