Insufficient expression of COL6A1 promotes the development of early-onset severe preeclampsia by inhibiting the APJ/AKT signaling pathway.

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Tác giả: Shuqi Chi, Yanmin Gong, Yanhui Jin, Yi Li, Xia Luo, Gonghua Qi, Wenxia Zhang

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: United States : Cell death discovery , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 741201

Early-onset severe preeclampsia (eosPE) is one of the most severe complications of pregnancy. To identify the genes related to the development of eosPE. We downloaded and integrated analyzed microarray data from GSE44711, GSE66273, and GSE74341, which contains the expression profile of placental tissues from patients with eosPE and healthy controls. Our analysis revealed that collagen type VI alpha 1 (COL6A1) was downregulated in the eosPE placenta compared to normal pregnancy. COL6A1 promoted the migration, invasion and tube formation ability of HTR8/SVneo cells, HUVECs and primary extravillous trophoblasts (EVTs). To explore the underlying mechanisms, we conducted transcriptome sequencing, which indicated that the Apelin/APJ signaling pathway was affected by COL6A1 knockdown. In addition, we found that APJ expression was lower in the placental tissue of patients with eosPE compared to healthy pregnancies. Inhibition of APJ suppressed the invasion, migration, and tube formation abilities of trophoblasts. We also observed that COL6A1 increased the levels of p-AKT and p-mTOR, while the APJ inhibitor ML221 impaired this effect. Furthermore, transwell and tube formation assays demonstrated that ML221 attenuated the capabilities enhanced by COL6A1, an effect that could be rescued by the AKT activator SC79. Overall, these findings indicate that insufficient expression of COL6A1 attenuates the migration, invasion, and endothelial-like tube formation of HTR8/SVneo cells and primary EVTs via the APJ/AKT/mTOR pathway, thereby promoting the development of eosPE.
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