Uteroplacental insufficiency decreases p53 serine-15 phosphorylation in term IUGR rat lungs

• DOI: 10.1152/ajpregu.00265.2005
• Publication Date: 2007-04-12T00:26:16Z
• Authors: E. A. O'Brien; V. Barnes; L. Zhao; R. A. McKnight; X. Yu; C. W. Callaway; L. Wang; J. C. Sun; M. J. Dahl; A. Wint; Z. Wang; T. M. McIntyre; K. H. Albertine; R. H. Lane
• Keywords: Mesenchyme; Intrauterine growth restriction; Placental insufficiency

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