The Downregulation of Placental Lumican Promotes the Progression of Preeclampsia

Abstract

Multiple pieces of evidence illustrate that impaired trophoblast function results in preeclampsia (PE), and migration/invasion of human trophoblast cells is stringently regulated by extracellular matrix (ECM) components. Many studies have indicated abnormal expressions of placental ECM components are associated with preeclampsia. However, the change and influence of lumican, a vital member of extracellular matrix (ECM) molecules, on trophoblast cells during preeclampsia remain unclear. This study examines the possibility that the roles of lumican in trophoblast cells contribute to PE. To address this issue, the expression of lumican in human placental tissues was observed using immunohistochemistry, fluorescence quantitative PCR, and Western blot technology. After the HTR-8/SVneo cell line was transfected with pcDNA3.1-human lumican, pGPU6-human lumican shRNA, and their negative controls, the impact of lumican on the HTR-8/SVneo cell line was investigated. Lumican was expressed in human placental tissues. Compared with the control group, its expression was significantly lower in PE placentas. Lumican downregulation inhibited cell proliferation significantly and reduced Bcl-2 expression, but increased P53 expression. These results indicate that the downregulation of placental lumican may drive PE development via promoting the downregulation of Bcl-2 expression and upregulation of P53.

The amniotic fluid proteome changes across gestation in humans and rhesus macaques

“…A separate study of amniotic fluid proteins using mass spectrometry and validation by ELISA identified lumican (LUM), apolipoprotein (APOA4), and kininogen-1 (KNG1) as biomarkers of preterm birth 38 . Lumican is a major proteoglycan expressed in the cornea and skin, as well as the placenta, where it is hypothesized to play a role in preeclampsia 39 . In our study, LUM was the 9th most abundant protein in human amniotic fluid and the 22nd most abundant in rhesus amniotic fluid, and was downregulated in both species with increasing gestational age.…”

Identification and validation of an angiogenesis-related signature associated with preeclampsia by bioinformatic analysis

“…[ 18 ] Recent studies have suggested that impaired trophoblast function can lead to PE, and human trophoblast cell migration/invasion is tightly regulated by the ECM. [ 19 ]…”

“…[18] Recent studies have suggested that impaired trophoblast function can lead to PE, and human trophoblast cell migration/invasion is tightly regulated by the ECM. [19] Despite increasing efforts to mine databases to identify molecular markers that can help diagnose and treat PE, ARGs in PE and immune infiltrates had not yet been investigated. Substantial evidence indicates that vascular disorder and deficient trophoblast invasion are involved in PE pathogenesis.…”

Screening and functional analysis of the differential peptides from the placenta of patients with healthy pregnancy and preeclampsia using placental peptidome

“…In trophoblasts, ECM thickness affects the production of mRNA and proteins related to fusion. Abnormal expression of placental ECM components is Frontiers in Genetics frontiersin.org associated with abnormal migration/invasion of human trophoblast cells (Romanowicz and Galewska 2011;Ma et al, 2020;Liu et al, 2021;Parameshwar et al, 2021). Consequently, PE may develop due to ECM changes.…”