Faculty Collaboration Database

Uteroplacental insufficiency decreases p53 serine-15 phosphorylation in term IUGR rat lungs. Am J Physiol Regul Integr Comp Physiol 2007 Jul;293(1):R314-22

Date

04/13/2007

Pubmed ID

17428897

DOI

10.1152/ajpregu.00265.2005

Scopus ID

2-s2.0-34447627844 (requires institutional sign-in at Scopus site)   30 Citations

Abstract

Intrauterine growth restriction (IUGR) increases the incidence of chronic lung disease (CLD). The molecular mechanisms responsible for IUGR-induced acute lung injury that predispose the IUGR infant to CLD are unknown. p53, a transcription factor, plays a pivotal role in determining cellular response to stress by affecting apoptosis, cell cycle regulation, and angiogenesis, processes required for thinning of lung mesenchyme. Because thickened lung mesenchyme is characteristic of CLD, we hypothesized that IUGR-induced changes in lung growth are associated with alterations in p53 expression and/or modification. We induced IUGR through bilateral uterine artery ligation of pregnant rats. Uteroplacental insufficiency significantly decreased serine-15-phosphorylated (serine-15P) p53, an active form of p53, in IUGR rat lung. Moreover, we found that decreased phosphorylation of lung p53 serine-15 localized to thickened distal air space mesenchyme. We also found that IUGR significantly decreased mRNA for targets downstream of p53, specifically, proapoptotic Bax and Apaf, as well as Gadd45, involved in growth arrest, and Tsp-1, involved in angiogenesis. Furthermore, we found that IUGR significantly increased mRNA for Bcl-2, an antiapoptotic gene downregulated by p53. We conclude that in IUGR rats, uteroplacental insufficiency induces decreased lung mesenchymal p53 serine-15P in association with distal lung mesenchymal thickening. We speculate that decreased p53 serine-15P in IUGR rat lungs alters lung phenotype, making the IUGR lung more susceptible to subsequent injury.

Author List

O'Brien EA, Barnes V, Zhao L, McKnight RA, Yu X, Callaway CW, Wang L, Sun JC, Dahl MJ, Wint A, Wang Z, McIntyre TM, Albertine KH, Lane RH

MESH terms used to index this publication - Major topics in bold

Animals
Animals, Newborn
Apoptosis
Blotting, Western
Cell Cycle
Female
Fetal Growth Retardation
Hyperplasia
Immunohistochemistry
Lung
Lung Diseases
Neovascularization, Physiologic
Phospholipids
Phosphorylation
Placental Insufficiency
Pregnancy
Protein Kinases
RNA
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Serine
Tumor Suppressor Protein p53