CLDN3 expression and function in pregnancy‑induced hypertension

Abstract

This aim of the present study was to investigate the expression and function of claudin 3 (CLDN3) in pregnancy-induced hypertension. The mRNA expression levels of CLDN3 in the placental tissue and peripheral blood of patients with pregnancy-induced hypertension were measured using reverse transcription-quantitative PCR. Human trophoblast HTR8/SVneo cells overexpressing CLDN3 were generated using a lentiviral vector. Cell Counting kit-8 (CCK-8) assay, flow cytometry, Transwell chamber assays, confocal laser scanning microscopy and western blot analysis were performed to detect cell proliferation, invasion, migration and apoptosis, in addition to matrix metalloproteinase (MMP) expression and ERK1/2 phosphorylation. The mRNA expression levels of CLDN3 were significantly reduced in the placental tissues and peripheral blood samples of patients with pregnancy-induced hypertension compared with healthy pregnant controls. CLDN3 overexpression significantly increased HTR8/SVneo cell proliferation, invasion and migration whilst reducing apoptosis. HTR8/SVneo cells overexpressing CLDN3 also exhibited increased myofiber levels, increased MMP-2 and MMP-9 expression and increased ERK1/2 signaling activity. CLDN3 downregulation may be associated with the pathogenesis of pregnancy-induced hypertension. In conclusion, CLDN3 promotes the proliferative and invasive capabilities of human trophoblast cells, with the underlying mechanisms possibly involving upregulation of MMP expression via the ERK1/2 signaling pathway.

Placental treatment with insulin-like growth factor 1 via nanoparticle differentially impacts vascular remodeling factors in guinea pig sub-placenta/decidua

“…The cell columns of the guinea pig subplacenta contain the progenitor trophoblast that become invasive trophoblast responsible for maternal vascular remodeling (Verkeste, Slangen et al, 1998). Under MNR conditions we demonstrated reduced Cldn5 expression, unsurprisingly since this has been shown to be down in cases of hypertension and preeclampia (Zhao, Qi et al, 2020;Adu-Gyamfi, Czika et al, 2021). Increased Ocln and Zo1 expression in the sub-placenta/decidua were seen suggesting strong cell adhesion and tight junctions which would not be conducive to EMT for proper invasion.…”

“…Through activation of the ERK1/2 pathway, claudin proteins upregulate matrix-metalloproteinases to help break down the extracellular matrix (ECM) as they invade into the maternal tissue and control permeability. mRNA levels of these claudin proteins have also been shown to be down in cases of hypertension and/or preeclampsia, suggesting a role in placental dysfunction ( Zhao, Qi et al, 2020 ). During normal placenta development ZO-1 and occludin are expressed in the proliferating trophoblasts and down regulation of these proteins is associated with the epithelial cell transformation that is necessary for proper invasion of EVTs ( Marzioni, Banita et al, 2001 ).…”

Advanced maternal age causes premature placental senescence and malformation via dysregulated α‐Klotho expression in trophoblasts

“…We then confirmed that CAM expression is required for the invasion of JAR cells, which is in accordance with previous reports noting that CDH4, CLDN3, and ITGAM are involved in the regulation of cell invasion. For example, Schumann et al reported that CLND3 was highly expressed in murine trophoblast giant cells and in human EVT cells and that it plays a role in the regulation of trophoblast invasion (Schumann et al., 2015; Zhao et al., 2020). Similarly, CDH4 deficiency impacts the invasion of human osteosarcoma cells (Tang et al., 2018), and epithelial ovarian cancer (EOC) invasion is mediated by ITGAM (Lyu et al., 2020).…”

The genetic risk factors for pregnancy‐induced hypertension: Evidence from genetic polymorphisms

“…5 Thereby, PIH is considered one of the main causes underlying the death of pregnant women, and searching for novel strategies for the prevention of PIH would significantly benefit maternal and neonatal outcome. 3 Although the etiology and pathophysiological mechanism of PIH have been gradually unveiled, the specific molecular mechanisms involved in PIH remain incompletely understood. 7,8 Several studies have suggested that the genetic risk factors involved in the renin-angiotensin system (RAS), endothelin system, inflammatory factors, and oxidative stress, are closely associated with PIH.…”

“…Moreover, fetuses of these PIH mothers are at higher risk of intrauterine growth retardation, prematurity, and intrauterine death 5 . Thereby, PIH is considered one of the main causes underlying the death of pregnant women, and searching for novel strategies for the prevention of PIH would significantly benefit maternal and neonatal outcome 3 . Although the etiology and pathophysiological mechanism of PIH have been gradually unveiled, the specific molecular mechanisms involved in PIH remain incompletely understood 7,8 .…”