Effects of postnatal dexamethasone treatment on mRNA expression profiles of genes related to alveolar development in an emphysema model in mice

Abstract

Emphysema can be induced in animals by postnatal treatment with dexamethasone (Dex) and such models have been widely used for various research. However, it is not clear what are the effects of Dex on assembly of alveolar elastic fibers in the emphysema model in mice. This study compared the expression profile of genes related to alveolar development between Dex treated and control mice during the treatment from postnatal day 3 (P3) to P14 with a 2-day break. From morphological observation of lung sections on P42, we confirmed the induction of emphysema in the treated mice. The mRNA expression level of fibrillin-1, which consists of microfibrils as a scaffold to form elastic fibers, and fibulin-5, which is a key protein reinforcing the fibers, reached maximum on P7 in control mice. However, in the Dex group, expression levels both types of mRNA were much lower with no clear expression peak. On the other hand, mRNA expression of tropoelastin, the main component in elastic fibers, reached maximum on P5 in the Dex group, which was 9 days earlier than in the control group. At this time, the amount of microfibrils might not be enough for tropoelastin to be deposited completely in Dex treated mice. This imbalance in the expression of tropoelastin and microfibril might interfere with the efficient formation of elastic fibers.