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Elevated trophoblastic Siglec6 contributes to the impairment of vascular endothelial cell functions by downregulating Wnt6/β-catenin signaling in preeclampsia

Authors :
Xiaonian Guan
Ming Yu
Linlin Wu
Jie Chen
Jianing Tong
Xiaoxia Wu
Aiqi Yin
Tianxia Xiao
Baobei Wang
Jian V. Zhang
Jianmin Niu
Source :
Archives of Biochemistry and Biophysics. 730:109396
Publication Year :
2022
Publisher :
Elsevier BV, 2022.

Abstract

Preeclampsia (PE), a systemic vascular disorder, is the leading cause of maternal and perinatal morbidity and mortality, and its pathogenesis has yet to be fully elucidated. Siglec6, a transmembrane protein, is highly expressed in human placental trophoblasts, and previous studies have shown that Siglec6 overexpression correlates with PE, but the role of Siglec6 during PE progression is unknown. Here, we demonstrated that the mRNA and protein expression levels of Siglec6 were upregulated in early-onset PE placentas compared with uncomplicated pregnancies, and Siglec6 was primarily located in syncytiotrophoblasts (STBs) and extravillous trophoblasts (EVTs). Moreover, our results showed that chemical reagent-induced HIF-1α accumulation promoted the mRNA and protein levels of Siglec6 in HTR8/SVneo and BeWo cells. Although Siglec6 overexpression did not affect HTR8/SVneo cell proliferation, migration, and invasion, the conditional medium derived from the Siglec6 overexpressed HTR8/SVneo cells (Siglec6-OE-CM) significantly impaired the proliferation, migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs). Subsequently, the transcriptome sequencing results revealed that Siglec6 overexpression led to the downregulation of Wnt6 in HTR8/SVneo cells, which was further confirmed by qPCR and ELISA. Recombinant human Wnt6 reversed Siglec6-OE-CM-mediated suppression of HUVEC functions by reactivating the Wnt/β-catenin signaling pathway. Altogether, our study found that elevated trophoblastic Siglec6 contributed to the impairment of vascular endothelial cell functions by downregulating Wnt6/β-catenin signaling.

Details

ISSN :
00039861
Volume :
730
Database :
OpenAIRE
Journal :
Archives of Biochemistry and Biophysics
Accession number :
edsair.doi.dedup.....a72a882ae06a800c9d8e30346da712b0
Full Text :
https://doi.org/10.1016/j.abb.2022.109396