IGFBP2 Modulates Trophoblast Function and Epithelial–Mesenchymal Transition in Preeclampsia via the PI3K/AKT Signaling Pathway

Background: Preeclampsia (PE) is a deadly obstetric complication in pregnant women leading to escalated rates of maternal and fetal mortality. Current research indicates that inadequate invasion of extravillous trophoblasts (EVTs) is a primary factor associated with the pathogenesis of PE. Insulin-l...

Full description

Saved in:
Bibliographic Details
Main Authors: Shengping Meng, Yanping Qin, Chunyan Lyu, Sumei Wang
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Current Issues in Molecular Biology
Subjects:
Online Access:https://www.mdpi.com/1467-3045/47/7/478
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849409578774560768
author Shengping Meng
Yanping Qin
Chunyan Lyu
Sumei Wang
author_facet Shengping Meng
Yanping Qin
Chunyan Lyu
Sumei Wang
author_sort Shengping Meng
collection DOAJ
description Background: Preeclampsia (PE) is a deadly obstetric complication in pregnant women leading to escalated rates of maternal and fetal mortality. Current research indicates that inadequate invasion of extravillous trophoblasts (EVTs) is a primary factor associated with the pathogenesis of PE. Insulin-like growth factor binding protein 2 (IGFBP2) plays a significant role in promoting cell migration, invasion, and angiogenesis. Researchers aim to investigate the clinical significance and elucidate the molecular mechanisms of IGFBP2 in the pathogenesis of preeclampsia. Methods: This study included 40 pregnant women categorized into 20 PE patients and 20 healthy controls. Expression levels of the mRNA were quantified using real-time quantitative polymerase chain reaction (qRT-PCR), and protein levels were assessed through Western blotting and immunofluorescence techniques. Moreover, the gain- and loss-of-function assays were conducted in human trophoblast cell line HTR-8/SVneo, and cellular models exhibiting overexpression and the knockdown of IGFBP2 were established. The proliferation, migration, and invasion of HTR-8/Svneo cells were determined using CCK8, wound-healing, and transwell assays, respectively. Results: The IGFBP2 was significantly downregulated, and the EMT was suppressed in the placental tissues of the PE patients. Functional experiments demonstrated that IGFBP2 enhanced the proliferation, invasion, and EMT of trophoblast cells activated through the PI3K/AKT signaling pathway. Conclusion: Our findings indicated that IGFBP2 enhances the proliferation, invasion, and EMT of trophoblast cells by activating the PI3K/AKT signaling pathway, serving as a potential therapeutic target in PE patients.
format Article
id doaj-art-ced85a477ae94dfd8a302b9c9119aaab
institution Kabale University
issn 1467-3037
1467-3045
language English
publishDate 2025-06-01
publisher MDPI AG
record_format Article
series Current Issues in Molecular Biology
spelling doaj-art-ced85a477ae94dfd8a302b9c9119aaab2025-08-20T03:35:27ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452025-06-0147747810.3390/cimb47070478IGFBP2 Modulates Trophoblast Function and Epithelial–Mesenchymal Transition in Preeclampsia via the PI3K/AKT Signaling PathwayShengping Meng0Yanping Qin1Chunyan Lyu2Sumei Wang3Department of Obstetrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, ChinaDepartment of Obstetrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, ChinaDepartment of Obstetrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, ChinaDepartment of Obstetrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, ChinaBackground: Preeclampsia (PE) is a deadly obstetric complication in pregnant women leading to escalated rates of maternal and fetal mortality. Current research indicates that inadequate invasion of extravillous trophoblasts (EVTs) is a primary factor associated with the pathogenesis of PE. Insulin-like growth factor binding protein 2 (IGFBP2) plays a significant role in promoting cell migration, invasion, and angiogenesis. Researchers aim to investigate the clinical significance and elucidate the molecular mechanisms of IGFBP2 in the pathogenesis of preeclampsia. Methods: This study included 40 pregnant women categorized into 20 PE patients and 20 healthy controls. Expression levels of the mRNA were quantified using real-time quantitative polymerase chain reaction (qRT-PCR), and protein levels were assessed through Western blotting and immunofluorescence techniques. Moreover, the gain- and loss-of-function assays were conducted in human trophoblast cell line HTR-8/SVneo, and cellular models exhibiting overexpression and the knockdown of IGFBP2 were established. The proliferation, migration, and invasion of HTR-8/Svneo cells were determined using CCK8, wound-healing, and transwell assays, respectively. Results: The IGFBP2 was significantly downregulated, and the EMT was suppressed in the placental tissues of the PE patients. Functional experiments demonstrated that IGFBP2 enhanced the proliferation, invasion, and EMT of trophoblast cells activated through the PI3K/AKT signaling pathway. Conclusion: Our findings indicated that IGFBP2 enhances the proliferation, invasion, and EMT of trophoblast cells by activating the PI3K/AKT signaling pathway, serving as a potential therapeutic target in PE patients.https://www.mdpi.com/1467-3045/47/7/478IGFBP2preeclampsiainvasionEMTPI3K/AKTtrophoblast
spellingShingle Shengping Meng
Yanping Qin
Chunyan Lyu
Sumei Wang
IGFBP2 Modulates Trophoblast Function and Epithelial–Mesenchymal Transition in Preeclampsia via the PI3K/AKT Signaling Pathway
Current Issues in Molecular Biology
IGFBP2
preeclampsia
invasion
EMT
PI3K/AKT
trophoblast
title IGFBP2 Modulates Trophoblast Function and Epithelial–Mesenchymal Transition in Preeclampsia via the PI3K/AKT Signaling Pathway
title_full IGFBP2 Modulates Trophoblast Function and Epithelial–Mesenchymal Transition in Preeclampsia via the PI3K/AKT Signaling Pathway
title_fullStr IGFBP2 Modulates Trophoblast Function and Epithelial–Mesenchymal Transition in Preeclampsia via the PI3K/AKT Signaling Pathway
title_full_unstemmed IGFBP2 Modulates Trophoblast Function and Epithelial–Mesenchymal Transition in Preeclampsia via the PI3K/AKT Signaling Pathway
title_short IGFBP2 Modulates Trophoblast Function and Epithelial–Mesenchymal Transition in Preeclampsia via the PI3K/AKT Signaling Pathway
title_sort igfbp2 modulates trophoblast function and epithelial mesenchymal transition in preeclampsia via the pi3k akt signaling pathway
topic IGFBP2
preeclampsia
invasion
EMT
PI3K/AKT
trophoblast
url https://www.mdpi.com/1467-3045/47/7/478
work_keys_str_mv AT shengpingmeng igfbp2modulatestrophoblastfunctionandepithelialmesenchymaltransitioninpreeclampsiaviathepi3kaktsignalingpathway
AT yanpingqin igfbp2modulatestrophoblastfunctionandepithelialmesenchymaltransitioninpreeclampsiaviathepi3kaktsignalingpathway
AT chunyanlyu igfbp2modulatestrophoblastfunctionandepithelialmesenchymaltransitioninpreeclampsiaviathepi3kaktsignalingpathway
AT sumeiwang igfbp2modulatestrophoblastfunctionandepithelialmesenchymaltransitioninpreeclampsiaviathepi3kaktsignalingpathway