Open Access

ARTICLE

UCK2 promotes the proliferation, migration, and invasion of trophoblast cells in preeclampsia by activating the STAT3 pathway

by WEI XIA¹, NING YANG², XIAOYAN FENG³, TING XIN¹, YONGLE JING¹, YUMING LI^4,*, CHENGZHI LU^1,5,*

1 Department of Cardiology, Tianjin First Central Hospital, Tianjin, 300192, China
2 Department of Hypertension, TEDA International Cardiovascular Hospital, Tianjin, 300457, China
3 Department of Dermatology, Tianjin Children’s Hospital, Tianjin, 300134, China
4 TEDA International Cardiovascular Hospital, Tianjin, 300457, China
5 School of Medicine, Nankai University, Tianjin, 300071, China

* Corresponding Authors: Chengzhi Lu, ; Yuming Li,

BIOCELL 2023, 47(4), 837-847. https://doi.org/10.32604/biocell.2023.026161

Received 19 August 2022; Accepted 15 November 2022; Issue published 08 March 2023

Abstract

Background: Preeclampsia (PE), characterized by hypertension and proteinuria, leads to serious maternal and infant complications. Uridine-cytidine kinase 2 (UCK2) belongs to the UCK family, a class of enzymes that catalyzes the conversion of uridine and cytidine to monophosphate form. However, the role of UCK2 in PE has not been reported. Methods: The expression of UCK2 was detected in the placenta of PE patients and N(ω)-nitro-L-arginine methyl esterinduced PE mouse model. Through forced up-regulation or down-regulation of UCK2 in vitro, we examined the effects of UCK2 on the proliferation, apoptosis, migration, and invasion of trophoblast cells. Stattic, the inhibitor of STAT3 pathway, was used to investigate whether the STAT3 pathway mediates the biological function of UCK2 in trophoblast cells. Results: The present study found that UCK2 showed low expression in the placenta of PE patients and PE mouse model. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and flow cytometry assays verified that up-regulation of UCK2 promoted the proliferation of trophoblast cells, while the silence of UCK2 suppressed cell proliferation. Besides, flow cytometry and TdT-mediated dUTP Nick-End Labeling assays demonstrated that knockdown of UCK2 resulted in apoptosis of trophoblast cells. The wound healing and transwell assays showed that the migration and invasion activities of the trophoblast cells were facilitated by the overexpression of UCK2 and were blocked by the silence of UCK2. Furthermore, the expression of phosphorylated STAT3 was increased with the upregulation of UCK2 and decreased with the inhibition of UCK2. When the STAT3 pathway was blocked by its inhibitor stattic, the promotion effects of UCK2 on trophoblast cells were suppressed. Conclusion: UCK2 promotes the proliferation, migration, and invasion of trophoblast cells, and these effects may be partly mediated by the activation of the STAT3 pathway.

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