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Updated: Jun 17, 2025
Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
Published on: August 3, 2018
Comprehensive Analysis and In Vitro Verification of Endothelial-Mesenchymal Transition-Related Genes in Moyamoya
Junsheng Li1,2, Qiheng He1,2, Zhiyao Zheng1,2
1Department of Neurosurgery, Fengtai District, Beijing Tiantan Hospital, Capital Medical University, No. 119 Nan Si Huan Xi Road, Beijing, 100070, China.
Abstract:
Moyamoya disease (MMD) is a rare, chronic, and progressive cerebrovascular disorder with unclear underlying causes and mechanisms. Previous studies suggest a potential involvement of endothelial-mesenchymal transition (EndMT) in the pathogenesis of MMD. This study aimed to explore the contribution of EndMT-related genes (ERGs) in MMD. Two datasets, GSE141022 and GSE157628, were integrated as the training set after batch effects removal. Differentially expressed ERGs were identified between MMD and control groups. Functional enrichment analysis and immune infiltration analysis were further performed. LASSO regression was used for hub MMD-related ERG selection. Consensus clustering was used for MMD subtype classification based on these hub MMD-related ERGs. Molecular characteristics between MMD subtypes were analyzed using WGCNA. PPI network was used to illuminate the genetic relationship. The hub MMD-related ERGs were validated in an independent testing set, GSE189993. The nomogram model was constructed and evaluated using ROC curves and calibration plots. Additionally, CCK-8, EdU, wound healing, and western blot were performed to confirm the function of the hub MMD-related ERGs. A total of 107 DE-ERGs were identified. Functional enrichment analysis showed these genes were associated with EndMT and immune response. The infiltrating levels of immune cells were commonly higher in the MMD group. LASSO regression identified 12 hub MMD-related ERGs, leading to the identification of two MMD subtypes. Four ERGs emerged as the final hub MMD-related ERGs after validation in the testing set, including CCL21, CEBPA, KRT18, and TNFRSF11A. The nomogram model exhibited excellent discrimination ability. In vitro experiments showed that CCL21, CEBPA, KRT18, and TNFRSF11A could promote proliferation, migration, and EndMT. This study investigated the potential role of EndMT in MMD and identified four hub MMD-related ERGs, providing potential therapeutic targets for MMD treatment.
Insights
This study identifies four key endothelial-mesenchymal transition-related genes (ERGs) involved in Moyamoya disease (MMD) pathogenesis. These genes, CCL21, CEBPA, KRT18, and TNFRSF11A, promote MMD progression and offer potential therapeutic targets.
Area of Science:
- * Neuroscience and Genetics
- * Vascular Biology and Pathology
Background:
- * Moyamoya disease (MMD) is a rare, progressive cerebrovascular disorder with unknown causes.
- * Endothelial-mesenchymal transition (EndMT) is hypothesized to play a role in MMD pathogenesis.
Purpose of the Study:
- * To investigate the contribution of EndMT-related genes (ERGs) in MMD.
- * To identify potential diagnostic and therapeutic targets for MMD.
Main Methods:
- * Integrated two gene expression datasets (GSE141022, GSE157628) for differential expression analysis of ERGs.
- * Employed LASSO regression for hub gene selection and consensus clustering for MMD subtype classification.
- * Validated hub ERGs in an independent dataset (GSE189993) and confirmed their function using in vitro assays.
Main Results:
- * Identified 107 differentially expressed ERGs associated with EndMT and immune response in MMD.
- * Discovered two distinct MMD subtypes based on hub ERGs.
- * Validated four hub ERGs (CCL21, CEBPA, KRT18, TNFRSF11A) that promote proliferation, migration, and EndMT in MMD.
Conclusions:
- * EndMT plays a significant role in MMD pathogenesis.
- * CCL21, CEBPA, KRT18, and TNFRSF11A are identified as key drivers of MMD progression.
- * These validated hub ERGs represent promising therapeutic targets for MMD treatment.
