SP1-mediated transcriptional activation of PTTG1 regulates the migration and phenotypic switching of aortic vascular smooth muscle cells in aortic dissection through MAPK signaling

Hu, Chuangjia; Huang, Weixing; Xiong, Nianling; Liu, Xiaoqiang

doi:10.1016/j.abb.2021.109007

Cited by 8 publications

(2 citation statements)

References 33 publications

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“… Dauer et al (2017) proved that inhibition of SP1 prevented endoplasmic reticulum homeostasis. Hu et al (2021) found that SP1 regulated migration and phenotype switching of VSMCs through the MAPK pathway in aortic dissections. Tang et al (2017) identified that microRNA-124 controlled VSMC phenotypic switching via SP1.…”

Section: Discussionmentioning

confidence: 98%

Comprehensive Analysis of Endoplasmic Reticulum Stress in Intracranial Aneurysm

Chen

Zhou

et al. 2022

Front. Cell. Neurosci.

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BackgroundAberrant endoplasmic reticulum stress (ERS) plays an important role in multiple cardiovascular diseases. However, their implication in intracranial aneurysms (IAs) remains unclear. We designed this study to explore the general expression pattern and potential functions of ERS in IAs.MethodsFive Gene Expression Omnibus (GEO) microarray datasets were used as the training cohorts, and 3 GEO RNA sequencing (RNA-seq) datasets were used as the validating cohorts. Differentially expressed genes (DEGs), functional enrichment, Lasso regression, logistic regression, ROC analysis, immune cell profiling, vascular smooth muscle cell (VSMC) phenotyping, weighted gene coexpression network analysis (WGCNA), and protein-protein interaction (PPI) analysis were applied to investigate the role of ERS in IA. Finally, we predicted the upstream transcription factor (TF)/miRNA and potential drugs targeting ERS.ResultsSignificant DEGs were majorly associated with ERS, autophagy, and metabolism. Eight-gene ERS signature and IRE1 pathway were identified during the IA formation. WGCNA showed that ERS was highly associated with a VSMC synthesis phenotype. Next, ERS-VSMC-metabolism-autophagy PPI and ERS-TF-miRNA networks were constructed. Finally, we predicted 9 potential drugs targeting ERS in IAs.ConclusionERS is involved in IA formation. Upstream and downstream regulatory networks for ERS were identified in IAs. Novel potential drugs targeting ERS were also proposed, which may delay IA formation and progress.

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Section: Discussionmentioning

confidence: 98%

Comprehensive Analysis of Endoplasmic Reticulum Stress in Intracranial Aneurysm

Chen

Zhou

et al. 2022

Front. Cell. Neurosci.

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“…The Sp1 transcription factor (SP1) was correlated with VEGFA, SYP and IL6. A study found that SP1 transcriptionally activates pituitary tumor-transforming gene 1 (PTTG1) to regulate the migration and phenotypic transformation of Human aortic vascular smooth muscle cells in AD through MAPK signaling [ 46 ]. Moreover, the abnormal expression of SP1 is also associated with the recurrence of meningioma [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of immune-related molecular markers in intracranial aneurysm (IA) based on machine learning and cytoscape-cytohubba plug-in

Zhong

Yue

et al. 2023

BMC Genom Data

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Background Intracranial aneurysm (IA) is a common cerebrovascular disease. The immune mechanism of IA is more complicated, and it is unclear so far. Therefore, it is necessary to continue to explore the immune related molecular mechanism of IA. Methods All data were downloaded from the public database. Limma package and ssGSEA algorithm was used to identify differentially expressed mRNAs (DEmRNAs) and analyze immune cell infiltration, respectively. Machine learning and cytoscape-cytohubba plug-in was used to identify key immune types and multicentric DEmRNAs of IA, respectively. Multicentric DEmRNAs related to key immune cells were screened out as key DEmRNAs by Spearman correlation analysis. Diagnostic models, competing endogenous RNA (ceRNA) regulatory network and transcription factor regulatory network were constructed based on key DEmRNAs. Meanwhile, drugs related to key DEmRNAs were screened out based on DGIdb database. The expression of key DEmRNAs was also verified by real time-PCR. Results In this study, 7 key DEmRNAs (NRXN1, GRIA2, SLC1A2, SLC17A7, IL6, VEGFA and SYP) associated with key differential immune cell infiltration (CD56bright natural killer cell, Immature B cell and Type 1 T helper cell) were identified. Functional enrichment analysis showed that VEGFA and IL6 may be involved in the regulation of the PI3K-Akt signaling pathway. Moreover, IL6 was also found to be enriched in cytokine-cytokine receptor interaction signaling pathway. In the ceRNA regulatory network, a large number of miRNAs and lncRNAs were found. In the transcription factor regulatory network, the transcription factor SP1 was correlated with VEGFA, SYP and IL6. It is also predicted that drugs related to key DEmRNAs such as CARBOPLATIN, FENTANYL and CILOSTAZOL may contribute to the treatment of IA. In addition, it was also found that SVM and RF models based on key DEmRNAs may be potential markers for diagnosing IA and unruptured intracranial aneurysm (UIA), respectively. The expression trend of key DEmRNAs verified by real-time PCR was consistent with the bioinformatics analysis results. Conclusion The identification of molecules and pathways in this study provides a theoretical basis for understanding the immune related molecular mechanism of IA. Meanwhile, the drug prediction and diagnosis model construction may also be helpful for clinical diagnosis and management.

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