Disruption of β-arrestins blocks glucocorticoid receptor and severely retards lung and liver development in mice

Mech Dev. Sep-Dec 2011;128(7-10):368-75. doi: 10.1016/j.mod.2011.07.003. Epub 2011 Jul 29.

Abstract

In this study, the role of β-arrestin 1 and β-arrestin 2 in fetal lung and liver development was examined using Arrb1(-/-)Arrb2(-/-) mouse embryos. β-Arrestin 1/2 dual-null mice died shortly after birth and morphological examination revealed an obvious pulmonary hypoplasia and severe hepatic impairment. Western blot analysis demonstrated that GR protein levels in Arrb1(-/-)Arrb2(-/-) lung and liver tissues were significantly decreased compared to wild type embryos. Expression of GR proteins was confirmed in the nuclei of type II pneumocytes of 18.5 day embryos (E18.5) by immunofluorescence. The production of hepatic glucose and mRNA level of gluconeogenic enzymes were dramatically reduced in E18.5 Arrb1(-/-)Arrb2(-/-) liver. These results suggest that GR is an important downstream effector of the β-arrestin signaling pathway involved in regulation of lung and liver development. However, no obvious changes in GR expression following in vitro modulation of β-arrestin 1/2 indicated the existence of an indirect regulatory relationship between GR and the β-arrestin signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alveolar Epithelial Cells / chemistry
  • Alveolar Epithelial Cells / metabolism
  • Animals
  • Arrestins / genetics*
  • Arrestins / metabolism*
  • Cell Line
  • Liver / embryology
  • Liver / enzymology
  • Liver / growth & development*
  • Liver / metabolism*
  • Lung / embryology
  • Lung / growth & development*
  • Lung / metabolism*
  • Mice
  • Mice, Knockout / genetics
  • Mice, Knockout / metabolism
  • Receptors, Glucocorticoid / metabolism*
  • Signal Transduction / physiology
  • beta-Arrestin 1
  • beta-Arrestin 2
  • beta-Arrestins

Substances

  • Arrb1 protein, mouse
  • Arrb2 protein, mouse
  • Arrestins
  • Receptors, Glucocorticoid
  • beta-Arrestin 1
  • beta-Arrestin 2
  • beta-Arrestins