Abnormal Trophoblast Invasion in Early-Onset Preeclampsia: The Involvement of Cystathionine β-Synthase, Specificity Protein 1 and microRNA-22

TL;DR

This study explores how certain proteins and genes are altered in early-onset preeclampsia, affecting trophoblast invasion during pregnancy.

Contribution

This is the first study to link miR-22 regulation of Sp1 with abnormal trophoblast invasion in early-onset preeclampsia.

Findings

MMPs 2, 9, CBS, and Sp1 were significantly reduced in early-onset preeclampsia patients.

TIMP-1 and TIMP-2 levels were elevated in early-onset preeclampsia participants.

miR-22 gene expression was upregulated in early-onset preeclampsia compared to controls.

Abstract

Objectives: To determine and compare the expression of matrix metalloproteinases (MMPs) 2, 9, tissue inhibitors of metalloproteinase (TIMPs) 1, 2, cystathionine β-synthase (CBS), specificity protein 1 (Sp1), and microRNA-22 (miR-22) in the early-onset preeclampsia (EOPE) patients and normotensive controls at both transcriptional and translational levels.

Methods: The study was carried out on EOPE women (n=50) as cases, and normotensive, non-proteinuric pregnant women (n=50) as controls, enrolled at the Department of Obstetrics and Gynaecology. Expression/levels of MMPs 2, 9, TIMPs 1, 2, CBS, Sp1, and miR-22 were determined in venous blood. Thirty cesarean-delivered placentae (15 each of EOPE patients and controls) were collected to analyze the expression/levels of the markers in the tissue.

Results: Significantly reduced mRNA and protein expression/levels of MMPs 2, 9, CBS, and Sp1, whereas elevated levels of TIMP-1 and TIMP-2 were observed in EOPE participants as compared to controls. The gene expression of miR-22 was found to be significantly upregulated in EOPE participants compared with controls.

Conclusions: This is the first study of its kind, which implies that insufficient trophoblastic invasion may be because of downregulation of MMPs 2, 9, CBS, Sp1, and concomitant upregulation of TIMPs 1, 2, both in the placentae collected at delivery and the circulating blood collected at diagnosis. The regulation of Sp1 by miR-22 in the EOPE participants as compared to controls was also evident by the expression of miR-22 assayed in the same set of samples.

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