Placenta Growth Factor Induces Invasion and Activates p70 during Rapamycin Treatment in Trophoblast Cells. (1st October 2014)

• Record Type: Journal Article
• Authors: Knuth, Allison; Liu, Lawrence; Nielsen, Halden; Merril, Daniel; Torry, Donald S.; Arroyo, Juan A.
• Is Part Of: American journal of reproductive immunology. Volume 73:Number 4(2015:Apr.)
• Page Start: 330
• Page End: 340
• Publication Date: 2014-10-01
• Subjects: Human reproduction -- Immunological aspects -- Periodicals; 616.69206
• DOI: 10.1111/aji.12327
• Languages: English
• ISSNs: 1046-7408

Abstract

<abstract abstract-type="main" id="aji12327-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="aji12327-sec-0001" sec-type="section"> <title>Problem</title> <p>Aberrant trophoblast invasion has been associated with human intrauterine growth restriction (IUGR) and preeclampsia (PE). Our objective was to determine placenta growth factor (PlGF)‐mediated regulation of cell invasion in trophoblast cells with reduced mammalian target of Rapamycin (mTOR) signaling.</p> </sec> <sec id="aji12327-sec-0002" sec-type="section"> <title>Method of study</title> <p>First trimester SW 71 trophoblast cells were subjected to invasion assays with the following conditions: 10% FBS, 10% FBS with Rapamycin, and 10% FBS with Rapamycin and PlGF. mTOR siRNA was also done in these cells. Western blots were performed on cell lysates with antibodies against phospho‐ and total mTOR, 70‐kDa ribosomal protein kinase I (p70), 4EBP1, extracellular regulated kinase (ERK), and phosphatidylinositol‐3 kinase (AKT).</p> </sec> <sec id="aji12327-sec-0003" sec-type="section"> <title>Results</title> <p>Compared to controls, trophoblast cells showed: (i) a 33% decrease in invasion following Rapamycin treatment, (ii) protection from decreased invasion following Rapamycin and PlGF treatment, (iii) a 31% decrease in mTOR phosphorylation with Rapamycin, (iv) increased phosphorylation of p70 (43%) with Rapamycin and PlGF, and (v) a 76% decrease in invasion following mTOR depletion.</p> </sec> <sec id="aji12327-sec-0004" sec-type="section"> <title>Conclusion</title> <p>We conclude that first trimester trophoblast invasion is functionally decreased when phosphorylation of mTOR is prevented and this decrease is recovered with the addition of PlGF. Mechanistically, this recovery involves the phosphorylation of p70 independent of mTOR.</p> </sec> </abstract>