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A Novel Murine Chronic Obstructive Pulmonary Disease Model and the Pathogenic Role of MicroRNA-21
Shengyang He1, Liqiu Li1, Shenghua Sun1
1Department of Respiratory Medicine, The Third Xiangya Hospital of Central South University, Changsha, China.
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.
Insights
A novel mouse model for chronic obstructive pulmonary disease (COPD) demonstrates that miR-21 levels indicate disease severity. Blocking miR-21 effectively ameliorates COPD symptoms, suggesting a potential early-stage treatment.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Animal Models
Background:
- Chronic obstructive pulmonary disease (COPD) pathogenesis remains incompletely understood.
- MicroRNAs (miRs) are implicated in COPD development.
- Existing animal models for COPD are time-consuming and expensive.
Purpose of the Study:
- To develop a novel, cost-effective mouse model for COPD.
- To investigate the role of miR-21 in COPD pathogenesis.
- To evaluate miR-21 as a potential therapeutic target.
Main Methods:
- A new combined method involving cigarette smoke exposure and extract injection was used to model COPD in mice.
- Lung function, body weight, and pathological changes were assessed.
- miR-21 levels were quantified using RT-qPCR, and its knockdown effects were studied.
Main Results:
- The novel model effectively replicated COPD-like changes, comparable to classic methods but faster and cheaper.
- Higher miR-21 levels correlated with increased inflammation and lung function decline.
- Knockdown of miR-21 significantly ameliorated COPD-related pathological and physiological changes.
Conclusions:
- The novel mouse model is a viable alternative for COPD research.
- miR-21 serves as a potential biomarker for COPD severity.
- Inhibition of miR-21 shows promise as an early-stage therapeutic strategy for COPD.
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