HMOX1 Participates in Pre-Eclampsia by Regulating the Proliferation, Apoptosis, and Angiogenesis Modulation Potential of Mesenchymal Stem Cells via VEGF.

Mesenchymal stem cells (MSCs) are involved in the pathogenesis of pre-eclampsia (PE). Heme oxygenase (HMOX) protects against placental cytotoxic injuries associated with PE. Here, we aimed to clarify the roles of HMOX1 in MSC proliferation and apoptosis, trophoblast cell migration, and regulation of angiogenesis, and assess its involvement in the pathogenesis of PE. HMOX1 and vascular endothelial growth factor (VEGF) expression levels in decidual tissues and decidua-derived MSCs (dMSCs) of healthy pregnant women and patients with PE were evaluated via quantitative reverse transcription-polymerase chain reaction and western blotting. Moreover, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and transwell assays were used to analyze the cell viability, apoptosis, and migration, respectively. The tube formation ability of human umbilical vein endothelial cells (HUVECs) was also evaluated. Compared to the healthy pregnant women, HMOX1 expression was upregulated in the decidual tissue and downregulated in the dMSCs of patients with PE. HMOX1 overexpression significantly increased dMSC proliferation, decreased cell apoptosis, and increased VEGF expression. Moreover, HMOX1-plasmid transfected dMSC culture supernatant promoted the migration of HTR-8/SVneo cells and improved angiogenesis by HUVECs. The opposite effects were observed in HMOX1-small interfering RNA-treated dMSCs cells. However, VEGF-siRNA reversed the effects of HMOX1-plasmid. HMOX1 is involved in the pathogenesis of PE by regulating the proliferation, apoptosis, and angiogenesis modulation potential of MSCs via VEGF, acting as a potential therapeutic target for PE.