PMID- 36370492 OWN - NLM STAT- MEDLINE DCOM- 20221213 LR - 20221219 IS - 1532-3102 (Electronic) IS - 0143-4004 (Linking) VI - 130 DP - 2022 Dec TI - PVT1/miR-145-5p/HK2 modulates vascular smooth muscle cells phenotype switch via glycolysis: The new perspective on the spiral artery remodeling. PG - 25-33 LID - S0143-4004(22)00435-0 [pii] LID - 10.1016/j.placenta.2022.10.010 [doi] AB - INTRODUCTION: Vascular smooth muscle cells (VSMC) switched from a contractile phenotype to a synthetic phenotype during the decidual spiral artery (SPAs) remodeling process. The lncRNA plasmacytoma variant translocation 1 (PVT1) and glucose metabolism have been found to regulate the VSMC phenotype switch. This study aimed to analyze the dynamic expression of PVT1 and glycolytic key enzymes hexokinase2 (HK2) at different remodeling stages in early human pregnancy and elucidate the underlying mechanism of the PVT1/miR-145-5p/HK2 axis involved in the spiral artery remodeling. METHODS: qRT-PCR, Western blot (WB) analysis, Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were used to detect the expression and localization of PVT1 and HK2 in decidual tissue. HA-VSMCs were transfected with specific siRNA, shRNA and plasmids to regulate corresponding genes. Extracellular lactate, cellular ATP, ROS, and intracellular NADPH levels were measured using the corresponding assay kits. Migration was measured by wound-healing and Transwell assays. Contractile phenotypic markers alpha-SMA, MYH11 with calponin and synthetic phenotypic markers OPN and vimentin were detected by WB. The PDC model was used to detect the degree of spiral arterial remodeling. RESULTS: PVT1 and HK2 were upregulated with gestational age (GA) increasing in decidual tissue during the early pregnancy. HK2 regulated the glycolytic activity and VSMC phenotype switch in vitro. PVT1 regulated the glycolytic activity and VSMC phenotype switch through HK2. PVT1 played a ceRNA role in regulating HK2 expression by sponging miR-145-5p. PVT1 and HK2 influenced spiral artery remodeling in the PDC model. DISCUSSION: PVT1 and HK2 were upregulated, and miR-145-5p was downregulated in decidua with the GA increasing. Meanwhile, the PVT1/miR-145-5p/HK2 axis may be involved in regulating the phenotypic switch and migratory capacity of VSMCs by affecting glycolysis in decidual SPAs remodeling. CI - Copyright (c) 2022. Published by Elsevier Ltd. FAU - Wu, Mengying AU - Wu M AD - Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Liu, Weifang AU - Liu W AD - Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Huang, Haixia AU - Huang H AD - Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Chen, Zhirui AU - Chen Z AD - Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Chen, Yangyang AU - Chen Y AD - Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Zhong, Yanqi AU - Zhong Y AD - Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Jin, Zhishan AU - Jin Z AD - Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Liu, Xiaoxia AU - Liu X AD - Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: xiehesummer@hust.edu.cn. FAU - Zou, Li AU - Zou L AD - Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: xiehezouli@hust.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221018 PL - Netherlands TA - Placenta JT - Placenta JID - 8006349 RN - 0 (MicroRNAs) RN - 0 (MIRN145 microRNA, human) RN - 0 (RNA, Long Noncoding) RN - 0 (RNA, Small Interfering) RN - 0 (PVT1 long-non-coding RNA, human) RN - EC 2.7.1.1 (HK2 protein, human) SB - IM EIN - Placenta. 2022 Dec 7;131:71-74. PMID: 36495833 MH - Female MH - Humans MH - Pregnancy MH - Arteries/metabolism MH - Cell Proliferation/genetics MH - Glycolysis/genetics MH - In Situ Hybridization, Fluorescence MH - *MicroRNAs/metabolism MH - Muscle, Smooth, Vascular/metabolism MH - Myocytes, Smooth Muscle/metabolism MH - Phenotype MH - *RNA, Long Noncoding/genetics MH - RNA, Small Interfering OTO - NOTNLM OT - Glycolysis OT - HK2 OT - PVT1 OT - Spiral artery remodeling OT - VSMC phenotype Switch COIS- Declaration of competing interest All authors declare no conflict of interest. EDAT- 2022/11/13 06:00 MHDA- 2022/12/07 06:00 CRDT- 2022/11/12 18:15 PHST- 2022/05/02 00:00 [received] PHST- 2022/10/01 00:00 [revised] PHST- 2022/10/14 00:00 [accepted] PHST- 2022/11/13 06:00 [pubmed] PHST- 2022/12/07 06:00 [medline] PHST- 2022/11/12 18:15 [entrez] AID - S0143-4004(22)00435-0 [pii] AID - 10.1016/j.placenta.2022.10.010 [doi] PST - ppublish SO - Placenta. 2022 Dec;130:25-33. doi: 10.1016/j.placenta.2022.10.010. Epub 2022 Oct 18.