Airway administration of dexamethasone, 3 ′-5 ′-cyclic adenosine monophosphate, and isobutylmethylxanthine facilitates compensatory lung growth in adult mice

Yusuke Takahashi, Yotaro Izumi, Mitsutomo Kohno, Masafumi Kawamura, Eiji Ikeda, Hiroaki Nomori

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The combination of dexa-methasone, 8-bromo-3 ′-5 ′-cyclic adenosine monophosphate, and isobutylmethylxanthine, referred to as DCI, has been reported to optimally induce cell differentiation in fetal lung explants and type II epithelial cells. DCI administration is also known to modulate the expression levels of many genes known to be involved in the facilitation of lung growth. Recently, we found that RNA silencing of thyroid transcription factor 1 (TTF-1) delayed compensatory lung growth. DCI is also known to induce TTF-1 expression in pulmonary epithelial cells. From these findings, we hypothesized that DCI administration may facilitate compensatory lung growth. In the present study, using a postpneumonectomy lung growth model in 9-wk-old male mice, we found that compensatory lung growth was significantly facilitated by airway administration of DCI immediately following left pneumonectomy, as indicated by the increase in the residual right lung dry weight index. TTF-1 expression was significantly elevated by DCI administration, and transient knockdown of TTF-1 attenuated the facilitation of compensatory lung growth by DCI. These results suggested that DCI facilitated compensatory lung growth, at least in part, through the induction of TTF-1. Morphological analyses suggested that DCI administration increased the number of alveoli, made each of them smaller, and produced a net increase in the calculated surface area of the alveoli per volume of lung. The effect of a single administration was maintained during the observation period, which was 28 days. DCI with further modifications may provide the material to potentially augment residual lung function after resection.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume300
Issue number3
DOIs
Publication statusPublished - 2011 Mar 1

Fingerprint

Cyclic AMP
Dexamethasone
Lung
Growth
Epithelial Cells
Pneumonectomy
RNA Interference
Cell Differentiation
Observation
thyroid nuclear factor 1
Weights and Measures

Keywords

  • Lung function
  • Thyroid transcription factor 1
  • Wheel-running test

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

Airway administration of dexamethasone, 3 ′-5 ′-cyclic adenosine monophosphate, and isobutylmethylxanthine facilitates compensatory lung growth in adult mice. / Takahashi, Yusuke; Izumi, Yotaro; Kohno, Mitsutomo; Kawamura, Masafumi; Ikeda, Eiji; Nomori, Hiroaki.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 300, No. 3, 01.03.2011.

Research output: Contribution to journalArticle

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