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.
Highlights
Continued development and industrialization has given rise to the expansion of various chronic diseases which, in turn, have significantly impacted families across the globe
They were divided into five groups of 10 mice each and subjected to five different modeling methods, as follows: (1) control group (CG), (2) novel combined method group (NCM, cigarette smoke (CS) exposure for 28 days combined with cigarette smoke extract (CSE) intraperitoneal injection), (3) short-term CS exposure group (SCSE, CS exposure for 28 days), (4) CSE intraperitoneal injection group (CSEII, 28 days CSE intraperitoneal injection), and (5) long-term CS exposure group (LCSE, CS exposure)
We evaluated the models on three levels: (1) body weight gain, (2) pathological changes, and (3) lung function
Summary
Continued development and industrialization has given rise to the expansion of various chronic diseases which, in turn, have significantly impacted families across the globe. Through the efforts of many researchers more COPD modeling methods have been suggested and demonstrated These alternate methods include: intranasal instillation of both elastase and LPS (Pera et al, 2014), only sulfur dioxide exposure (Wagner et al, 2006), inhalation of ovalbumin dry powder (Misaka et al, 2009), intravenous injection of hyaluronidase (Tazaki et al, 2006), genetic manipulation (Baron et al, 2012), intraperitoneal injection with xenogeneic endothelial cells (Taraseviciene-Stewart et al, 2005), and intraperitoneal injection with CSE (He et al, 2013). The pathogeneses of these alternate methods may not be clinically relevant and potentially lead to bias conclusions
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