1141610241 Altered expression of HuR, an mRNA stabilizing protein, mediates aberrant Placenta Growth Factor (PlGF) expression in preeclampsia

Abstract

Background: Control of mRNA stability is an essential regulatory process in eukaryotic gene expression. HuR, a 3’UTR mRNA binding protein, can protect AU‐rich mRNA from degradation in response to stresses. PlGF, an angiogenic growth factor, contains two consensus AU‐rich sites suggesting that under normal conditions HuR may protect PlGF mRNA from degradation. Trophoblast expression of PlGF is significantly decreased in preeclampsia and by hypoxia in vitro. We hypothesize that decreased levels of cytoplasmic HuR may contribute to decreased PlGF expression in hypoxic and preeclamptic trophoblast.Methods: Western blots were used to determine relative effects of in vitro hypoxia on HuR protein expression and subcellular localization in trophoblast. Immunohistochemistry was used to compare HuR expression patterns in trophoblast of preeclamptic and normal placentae.Results: Cytoplasmic expression of HuR was decreased 1.4 fold in the cytoplasm and 1.2 fold in the nucleus of JEG3 cells. A shift in HuR was more apparent in primary trophoblast with a greater than 2‐fold decrease in the cytoplasm and a 1.4 fold decrease in the nucleus following 24 hr of hypoxia. Immunohistochemical analyses detected HuR expression in near term trophoblast in situ. However, this technical approach did not detect a significant change in HuR expression between normal and preeclamptic trophoblast.Conclusions: HuR expression is decreased in hypoxic trophoblast, at least in vitro, which may provide a causal link to decreased PlGF mRNA expression. Down regulation of trophoblast PlGF expression is thought to contribute to the pathophysiology associated with preeclampsia including the relative lack of perfusion of the placenta and systemic renal effects.