Restored microRNA-133a-3p or Depleted PSAT1 Restrains Endothelial Cell Damage-Induced Intracranial Aneurysm Via Suppressing the GSK3β/β-Catenin Pathway

Abstract It is unclear about the functional role of microRNA-133a-3p (miR-133a-3p) in intracranial aneurysm (IA). Hence, the aim of the present study was to investigate the regulatory role of miR-133a-3p on the regulation of vascular endothelial injury-induced IA through phosphoserine aminotransfera...

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Main Authors: Qiang Jia, Shixin Yan, Jie Huang, Shixin Xu
Format: Article
Language:English
Published: SpringerOpen 2020-09-01
Series:Nanoscale Research Letters
Subjects:
Online Access:http://link.springer.com/article/10.1186/s11671-020-03396-9
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author Qiang Jia
Shixin Yan
Jie Huang
Shixin Xu
author_facet Qiang Jia
Shixin Yan
Jie Huang
Shixin Xu
author_sort Qiang Jia
collection DOAJ
description Abstract It is unclear about the functional role of microRNA-133a-3p (miR-133a-3p) in intracranial aneurysm (IA). Hence, the aim of the present study was to investigate the regulatory role of miR-133a-3p on the regulation of vascular endothelial injury-induced IA through phosphoserine aminotransferase 1 (PSAT1)/glycogen synthase kinase 3β (GSK3β)/β-catenin signaling pathway. Normal intracranial arteriole tissues and IA tissues were gathered from patients with brain trauma and IA. The expression of miR-133a-3p, PSAT1, GSK3β, and β-catenin in tissues was determined by RT-qPCR and western blot analysis. The endothelial cells (ECs) of the human IA were cultured and treated with miR-133a-3p mimic and si-PSAT1 to determine their functions in endothelial cell migration, apoptosis, and proliferation. The expression of miR-133a-3p, PSAT1, GSK3β, β-catenin, Ki-67, CyclinD1, Bax, and Bcl-2 in ECs were tested by RT-qPCR or western blot analysis. Moreover, IA rat model was established to detect the pathological changes and the expression of miR-133a-3p, PSAT1, GSK3β, β-catenin, VEGF, and MMP-9 in IA tissues in vivo. Expression of miR-133a-3p was related to the number and size of IA. MiR-133a-3p expression was deceased and the PSAT1, GSK3β, and β-catenin expression was raised in IA. Restored miR-133a-3p and depleted PSAT1 alleviated the pathological change; reduced PSAT1, GSK3β, and β-catenin expression in IA; suppressed apoptosis and advanced proliferation and migration of IA ECs, as well as reduced VEGF and MMP-9 expression in IA tissues in vivo. Our study suggests that overexpression of miR-133a-3p or downregulation of PSAT1 restrains endothelial cell damage and advances endothelial cell proliferation via inhibiting the GSK3β/β-catenin pathway in IA. MiR-133a-3p might be a potential candidate marker and therapeutic target for IA.
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spelling doaj.art-f2a496a094dd4c92a3ac141c31f3cd6a2023-09-02T13:06:10ZengSpringerOpenNanoscale Research Letters1556-276X2020-09-0115111510.1186/s11671-020-03396-9Restored microRNA-133a-3p or Depleted PSAT1 Restrains Endothelial Cell Damage-Induced Intracranial Aneurysm Via Suppressing the GSK3β/β-Catenin PathwayQiang Jia0Shixin Yan1Jie Huang2Shixin Xu3Department of Neurosurgery, Tianjin Huanhu HospitalDepartment of Radiology, Tianjin Huanhu HospitalDepartment of Neurology, Cangzhou People’s HospitalClinical Laboratory, First Teaching Hospital of Tianjin University of Traditional Chinese MedicineAbstract It is unclear about the functional role of microRNA-133a-3p (miR-133a-3p) in intracranial aneurysm (IA). Hence, the aim of the present study was to investigate the regulatory role of miR-133a-3p on the regulation of vascular endothelial injury-induced IA through phosphoserine aminotransferase 1 (PSAT1)/glycogen synthase kinase 3β (GSK3β)/β-catenin signaling pathway. Normal intracranial arteriole tissues and IA tissues were gathered from patients with brain trauma and IA. The expression of miR-133a-3p, PSAT1, GSK3β, and β-catenin in tissues was determined by RT-qPCR and western blot analysis. The endothelial cells (ECs) of the human IA were cultured and treated with miR-133a-3p mimic and si-PSAT1 to determine their functions in endothelial cell migration, apoptosis, and proliferation. The expression of miR-133a-3p, PSAT1, GSK3β, β-catenin, Ki-67, CyclinD1, Bax, and Bcl-2 in ECs were tested by RT-qPCR or western blot analysis. Moreover, IA rat model was established to detect the pathological changes and the expression of miR-133a-3p, PSAT1, GSK3β, β-catenin, VEGF, and MMP-9 in IA tissues in vivo. Expression of miR-133a-3p was related to the number and size of IA. MiR-133a-3p expression was deceased and the PSAT1, GSK3β, and β-catenin expression was raised in IA. Restored miR-133a-3p and depleted PSAT1 alleviated the pathological change; reduced PSAT1, GSK3β, and β-catenin expression in IA; suppressed apoptosis and advanced proliferation and migration of IA ECs, as well as reduced VEGF and MMP-9 expression in IA tissues in vivo. Our study suggests that overexpression of miR-133a-3p or downregulation of PSAT1 restrains endothelial cell damage and advances endothelial cell proliferation via inhibiting the GSK3β/β-catenin pathway in IA. MiR-133a-3p might be a potential candidate marker and therapeutic target for IA.http://link.springer.com/article/10.1186/s11671-020-03396-9Intracranial aneurysmMicroRNA-133a-3pPSAT1
spellingShingle Qiang Jia
Shixin Yan
Jie Huang
Shixin Xu
Restored microRNA-133a-3p or Depleted PSAT1 Restrains Endothelial Cell Damage-Induced Intracranial Aneurysm Via Suppressing the GSK3β/β-Catenin Pathway
Nanoscale Research Letters
Intracranial aneurysm
MicroRNA-133a-3p
PSAT1
title Restored microRNA-133a-3p or Depleted PSAT1 Restrains Endothelial Cell Damage-Induced Intracranial Aneurysm Via Suppressing the GSK3β/β-Catenin Pathway
title_full Restored microRNA-133a-3p or Depleted PSAT1 Restrains Endothelial Cell Damage-Induced Intracranial Aneurysm Via Suppressing the GSK3β/β-Catenin Pathway
title_fullStr Restored microRNA-133a-3p or Depleted PSAT1 Restrains Endothelial Cell Damage-Induced Intracranial Aneurysm Via Suppressing the GSK3β/β-Catenin Pathway
title_full_unstemmed Restored microRNA-133a-3p or Depleted PSAT1 Restrains Endothelial Cell Damage-Induced Intracranial Aneurysm Via Suppressing the GSK3β/β-Catenin Pathway
title_short Restored microRNA-133a-3p or Depleted PSAT1 Restrains Endothelial Cell Damage-Induced Intracranial Aneurysm Via Suppressing the GSK3β/β-Catenin Pathway
title_sort restored microrna 133a 3p or depleted psat1 restrains endothelial cell damage induced intracranial aneurysm via suppressing the gsk3β β catenin pathway
topic Intracranial aneurysm
MicroRNA-133a-3p
PSAT1
url http://link.springer.com/article/10.1186/s11671-020-03396-9
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