SRPK1 gene silencing promotes vascular smooth muscle cell proliferation and vascular remodeling via inhibition of the PI3K/Akt signaling pathway in a rat model of intracranial aneurysms

Li, Xinguo; Wang, Yibao

doi:10.1111/cns.13043

Cited by 36 publications

(24 citation statements)

References 43 publications

(88 reference statements)

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“…The PI3K-Akt signaling pathway is activated by various types of cellular stimuli or toxic insults, and regulates fundamental cellular functions such as transcription, translation, proliferation, growth, and survival. Dysregulation in the PI3K-Akt signaling pathway is implicated in various diseases such as cancer, type 2 diabetes mellitus, and IA [ 7 , 30 , 31 ]. Previous research reported that activation of PI3K-Akt signaling pathway promoted proliferation of vascular smooth muscle cells which were found to be involved in aortic aneurysms [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Construction of competitive endogenous RNA network reveals regulatory role of long non-coding RNAs in intracranial aneurysm

Pan

Yang

et al. 2021

BMC Neurosci

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Background Rupture of intracranial aneurysm (IA) is the main cause of devastating subarachnoid hemorrhage, which urges our understanding of the pathogenesis and regulatory mechanisms of IA. However, the regulatory roles of long non-coding RNAs (lncRNAs) in IA is less known. Results We processed the raw SRR files of 12 superficial temporal artery (STA) samples and 6 IA samples to count files. Then the differentially expressed (DE) mRNAs, miRNAs, and lncRNAs between STAs and IAs were identified. The enrichment analyses were performed using DEmRNAs. Next, a lncRNA-miRNA-mRNA regulatory network was constructed using integrated bioinformatics analysis. In summary, 341 DElncRNAs, 234 DEmiRNAs, and 2914 DEmRNAs between the STA and IA. The lncRNA-miRNA-mRNA regulatory network of IA contains 91 nodes and 146 edges. The subnetwork of hub lncRNA PVT1 was extracted. The expression level of PVT1 was positively correlated with a majority of the mRNAs in its subnetwork. Moreover, we found that several mRNAs (CCND1, HIF1A, E2F1, CDKN1A, VEGFA, COL1A1 and COL5A2) in the PVT1 subnetwork served as essential components in the PI3K-Akt signaling pathway, and that some of the non-coding RNAs (ncRNAs) (PVT1, HOTAIR, hsa-miR-17, hsa-miR-142, hsa-miR-383 and hsa-miR-193b) interacted with these mRNAs. Conclusion Our annotations noting ncRNA’s role in the pathway may uncover novel regulatory mechanisms of ncRNAs and mRNAs in IA. These findings provide significant insights into the lncRNA regulatory network in IA.

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Section: Discussionmentioning

confidence: 99%

Construction of competitive endogenous RNA network reveals regulatory role of long non-coding RNAs in intracranial aneurysm

Pan

Yang

et al. 2021

BMC Neurosci

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“…Li et al have proven that PI3K/Akt signaling pathway has effect on the production of IA in rat model. [ 25 ] The involvement of this pathway in other kinds of aneurysm such as abdominal aortic aneurysm and thoracic aortic aneurysm is also detected by different groups. [ 26 , 27 ] Based on existing knowledge, we speculate that PI3K/Akt may affect IA via following ways.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of microRNA profiles and identification of microRNA-mRNA network and biological markers in intracranial aneurysm

Zhao

Qian

2020

Medicine

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Intracranial aneurysm (IA) is a kind of cerebrovascular disorder, which may result in the subarachnoid hemorrhage with high lethality and disability. The purpose of this study was to reveal the pathogenesis and identify novel biomarkers in IA. We processed the raw microRNA (miRNA) expression profile data of IA obtained from Gene Expression Omnibus. Then weighted correlation network analysis was performed to identify the hub miRNAs in IA. Target genes of hub miRNAs were predicted using multiR package. In addition, a protein-protein network as well as miRNA-mRNA network was constructed and functional and pathway enrichment analyses were done. Finally, the prediction value of hub miRNAs in IA was tested in validation set. Two modules that had relation with IA were identified and 10 hub miRNAs in each module with higher gene-module association were selected. The protein-protein network and miRNA-mRNA network contained 243 nodes and 1496 edges. Functional and pathway enrichment analyses showed that they were mainly enriched in cell cycle, cell proliferation, and PI3K/Akt signaling pathways. Besides, hsa-miR-191-3p, hsa-miR-423-5p, hsa-miR-424-5p, hsa-miR-425-3p were proven to be valuable in prediction IA occurrence. In a word, this study reveals hub miRNAs, target genes and pathways potentially participating in formation and development of IA and screens out some candidate biomarkers. Our findings provide some new perspectives for research and treatment of IA.

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“…The pro-inflammatory phenotype is characterized by reduced levels of the contractile elements of SMCs, accompanied by increased levels of transcription factors involved in promoting inflammation, recruitment of reactive oxygen species, and matrix remodeling 9–11 . This SMC phenotype switch has been identified as potentially promoting aneurysm progression 12–18 .…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Smooth Muscle Cells Induce Endothelial Cell Alterations to Influence Cerebral Aneurysm Progression via Regulation of Integrin and VEGF Expression

et al. 2018

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Cerebral aneurysm growth is characterized by vessel wall frailness, although the underlying cellular mechanisms are unclear. Here, we examined the relationship between inflammatory smooth muscle cells (SMCs) and endothelial cells (ECs) in cerebral aneurysms, including the mechanisms underlying inflammatory SMC-induced changes in ECs. Five saccular cerebral aneurysms were collected and five temporal artery samples were used as controls. Cells and cytokines were detected by immunohistochemistry and TUNEL (transferase dUTP nick end labeling) assays performed to evaluate apoptosis. Human umbilical vein endothelial cells (HUVECs) were seeded on collagen I, IV, and VI-coated plates for cell adhesion assays and inflammatory SMCs (iSMCs) were established by culture in flexible silicone chambers subjected to cyclic mechanical stretch. HUVECs were cultured in iSMC-conditioned medium, followed by evaluation of their viability, apoptosis, and function, and determination of VEGF (vascular endothelial growth factor) -A and integrin levels by western blotting. Aneurysm tissue contained fewer SMCs and lacked ECs. In aneurysm walls, more matrix metalloproteinase (MMP) -1, MMP-3, and apoptotic cells were detected, accompanied by decreased collagen IV and VI levels. Cell adhesion assays revealed that more HUVECs were attached in collagen IV and VI-coated plates compared with controls. iSMC-conditioned medium significantly reduced HUVEC viability and apoptosis showed an increased trend; however, the difference was not significant. iSMC medium also reduced tube formation and migration of HUVECs. Moreover, iSMC medium reduced HUVEC expression of VEGF-A, integrin α1, integrin α2, and integrin β. Our data demonstrate a lack of SMCs and ECs in aneurysm walls, accompanied by elevated MMP and decreased collagen levels. In vitro assays showed that iSMCs induced reduction in EC adhesion, and caused EC dysfunction. Understanding of the relationships among SMC, EC, and collagens during aneurysm progression provides an additional therapeutic option for prevention of cerebral aneurysm progression.

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SRPK1 gene silencing promotes vascular smooth muscle cell proliferation and vascular remodeling via inhibition of the PI3K/Akt signaling pathway in a rat model of intracranial aneurysms

Abstract: Our results show that siRNA-mediated silencing of SRPK1 gene inhibits VSMC apoptosis, and increases VSMCs proliferation and vascular remodeling in IA via the PI3 K/Akt signaling pathway. Our findings provide a novel intervention target for the molecular treatment of IA.

Cited by 36 publications

References 43 publications

Construction of competitive endogenous RNA network reveals regulatory role of long non-coding RNAs in intracranial aneurysm

Construction of competitive endogenous RNA network reveals regulatory role of long non-coding RNAs in intracranial aneurysm

Bioinformatics analysis of microRNA profiles and identification of microRNA-mRNA network and biological markers in intracranial aneurysm

Inflammatory Smooth Muscle Cells Induce Endothelial Cell Alterations to Influence Cerebral Aneurysm Progression via Regulation of Integrin and VEGF Expression

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