Open AccessPotential regulatory network in the PSG10P/miR‐19a‐3p/IL1RAP pathway is possibly involved in preeclampsia pathogenesis
Author(s) -
Wang Nan,
Li Ruizhen,
Xue Min
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13985
Subject(s) - trophoblast , pathogenesis , preeclampsia , biology , microrna , luciferase , microbiology and biotechnology , viability assay , reporter gene , hypoxia (environmental) , messenger rna , in vivo , andrology , placenta , cell culture , immunology , gene expression , fetus , medicine , transfection , gene , chemistry , pregnancy , genetics , organic chemistry , oxygen
Preeclampsia ( PE ), a pregnancy‐specific disorder, is a leading cause of perinatal maternal‐fetal mortality and morbidity. Impaired cell migration and invasion of trophoblastic cells and an imbalanced systemic maternal inflammatory response have been proposed as potential mechanisms of PE pathogenesis. Comparative analysis between PE placentas and normal placentas profiled differentially expressed mi RNA s, lnc RNA s, and mRNA s, including miR‐19a‐3p (mi RNA ), PSG 10P (lnc RNA ), and IL 1 RAP ( mRNA ). This study was conducted to investigate their potential roles in PE pathogenesis. The expression of miR‐19a‐3p, PSG 10P, and IL 1 RAP was examined in PE and normal placentas using RT ‐ qPCR . An in vitro experiment was performed in human trophoblast HET 8/ SV neo and TEV ‐1 cells cultured in normoxic and hypoxic conditions. MiR‐19a‐3p targets were identified using Targetscan, miRanda, and PicTar analysis as well as luciferase reporter assays. The mouse model of PE was conducted using sF lt‐1 for in vivo tests. Lower levels of miR‐19a‐3p, but higher levels of PSG 10P and IL 1 RAP were observed in PE placentas and the trophoblast cells in hypoxia. Luciferase reporter assays confirmed that PSG 10P and IL 1 RAP were both direct targets of miR‐19a‐3p. Exposure to hypoxia inhibited cell viability, migration, and invasion of HET 8/ SV neo and TEV ‐1 cells. Knocking out PSG 10P and IL 1 RAP or overexpressing miR‐19a‐3p rescued the inhibition caused by hypoxia. In vivo experiments showed that IL 1 RAP promoted the expression of caspase‐3, a key apoptosis enzyme, but inhibited MMP 9, which is responsible for degrading the extracellular matrix, suggesting a significant role of IL 1 RAP in cell proliferation, migration, and invasion. miR‐19a‐3p, PSG 10P, and IL 1 RAP were all found to be involved in PE pathogenesis. With a common targeting region in their sequences, a regulatory network in the PSG 10P/miR‐19a‐3p/ IL 1 RAP pathway may contribute to PE pathogenesis during pregnancy.