title: Disruption of β-arrestins blocks glucocorticoid receptor and severely retards lung and liver development in mice.
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.
authors.affiliation: Fujian Key Laboratory of Developmental and Neuro Biology, College of Life Sciences, Fujian Normal University, Fuzhou, PR China. biozmf@163.com
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Zhang
authors.forename: Hongqi
authors.initials: H
authors.lastname: Teng
authors.forename: Jueping
authors.initials: J
authors.lastname: Shi
authors.forename: Yanding
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D056809:Alveolar Epithelial Cells / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D019390:Arrestins / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D008099:Liver / Q000196:embryology / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism*; D008168:Lung / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D000071559:beta-Arrestin 1; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
chemical_list: C000605255:Arrb1 protein, mouse; C000605258:Arrb2 protein, mouse; D019390:Arrestins; D011965:Receptors, Glucocorticoid; D000071559:beta-Arrestin 1; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins