Auto-measure emphysematous parameters and pathophysiological gene expression profiles in experimental mouse models of acute and chronic obstructive pulmonary diseases

• Main Authors: Ryunosuke Nakashima (Author), Shunsuke Kamei (Author), Hirofumi Nohara (Author), Haruka Fujikawa (Author), Kasumi Maruta (Author), Taisei Kawakami (Author), Yuka Eto (Author), Noriki Takahashi (Author), Mary Ann Suico (Author), Toru Takeo (Author), Naomi Nakagata (Author), Hirofumi Kai (Author), Tsuyoshi Shuto (Author)
• Format: Book
• Published: Elsevier, 2019-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Pulmonary emphysema, inflammation and senescence-like phenotype are pathophysiological characteristics of chronic obstructive pulmonary disease (COPD). Recently, a murine model of COPD has been established by inducing airway-specific overexpression of epithelial Na+ channel β subunit (βENaC-Tg mice). However, little is known about the histological and biochemical differences between βENaC-Tg mice and an existing acute emphysematous mouse model (elastase-induced model). Here, we first utilized whole lung image-based quantification method for histological analysis to determine auto-measure parameters, including alveolar area, alveolar perimeter, (major axis + minor axis)/2 and Feret diameter. Even though the extent of emphysema was similar in both models, the coefficient of variation (CV) of all histological parameters was smaller in βENaC-Tg mice, indicating that βENaC-Tg mice show homogeneous emphysema as compared with elastase-induced acute model. Expression analysis of lung tissue RNAs further revealed that elastase-induced model exhibits transient changes of inflammation markers (Kc, Il-6, Lcn2) and senescence-related markers (Sirt1, p21) at emphysema-initiation stage (1 day), which does not last until emphysema-manifestation stage (3 weeks); while the up-regulation is stable at emphysema-manifestation stage in βENaC-Tg mice (14-week old). Thus, these studies demonstrate that βENaC-Tg mice exhibit diffuse-type emphysema with stable expression of inflammatory and senescence-like markers. Keywords: Chronic pulmonary obstructive disease (COPD), Epithelial Na+ channel (ENaC), Emphysema, Auto-measure parameters, Senescence

Item Description

1347-8613
10.1016/j.jphs.2019.01.011