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Published on: September 19, 2016
Blocking CCR10 Expression Activates m6A Methylation and Alleviates Vascular Endothelial Cell Injury
Zengding Zhou1, Huizhong Yang1, Xiqiao Wang1
1Department of Burn Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, 200025 Shanghai, China.
Insights
Blocking C-C motif chemokine receptor 10 (CCR10) activates N6-methyladenosine (m6A) methylation, improving cell activity and reducing inflammation in cardiovascular disease models. This finding offers a potential breakthrough for treating cardiovascular diseases (CVDs).
Area of Science:
- Cardiovascular research
- Molecular biology
- Genomics
Background:
- Cardiovascular disease (CVD) poses a significant global health risk.
- Human dermal microvascular endothelial cells (HDMECs) play a crucial role in vascular health.
- Understanding molecular mechanisms underlying endothelial cell injury is vital for CVD treatment.
Purpose of the Study:
- To investigate genome-wide changes in injured HDMECs using RNA sequencing (RNA-Seq).
- To identify key genes influencing N6-methyladenosine (m6A) methylation in cardiovascular disease.
- To explore potential therapeutic targets for CVDs.
Main Methods:
- RNA-sequencing (RNA-Seq) to analyze differentially expressed genes (DEGs) in endotoxin-injured HDMECs.
- Selection of DEGs associated with m6A methylation for functional analysis.
- Cellular assays including scratch, western blotting, and ELISA to assess cell migration, angiogenesis, and inflammation.
Main Results:
- RNA-Seq identified 20 DEGs, with C-C motif chemokine receptor 10 (CCR10) being significantly upregulated.
- Elevated CCR10 expression correlated with reduced m6A methylation in injured HDMECs.
- Blocking CCR10 enhanced m6A methylation, promoted cell activity, angiogenesis, and reduced inflammation.
Conclusions:
- Blocking CCR10 expression activates m6A methylation and alleviates HDMEC injury.
- CCR10 inhibition demonstrates potential for promoting cell activity and reducing inflammatory responses.
- Targeting CCR10 offers a promising therapeutic strategy for cardiovascular diseases.
Background:
Cardiovascular disease, one of the most common types of disease in clinical practice today, carries a very high risk of disability and death. This research aims to examine genome-wide changes in injured human dermal microvascular endothelial cells (HDMECs) using the Ribonucleic Acid sequencing (RNA-Seq) technique, and to search for key genes influencing N6-methyladenosine (m6A) methylation, thus gaining new insights into future clinical diagnosis and treatment of cardiovascular diseases (CVDs) and laying a foundation for follow-up research.
Methods:
Impaired HDMECs (injury group), established by endotoxin intervention, were analyzed by RNA-Seq for differentially expressed genes (DEGs) relative to normal HDMECs (control group). Then, DEGs that might be associated with m6A methylation were selected for expression blocking to observe m6A methylation alterations. The migration, angiogenesis, and inflammatory response of damaged HDMECs were detected by cell scratch assay, western blotting, and Enzyme-linked Immunosorbent Assay (ELISA) experiments, respectively.
Results:
In this study, 20 DEGs were screened out from the two groups by RNA-Seq, of which 17 were up-regulated and 3 were down-regulated. The C-C motif chemokine receptor 10 (CCR10) was selected for subsequent analysis. Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) identified elevated CCR10 expression and reduced m6A methylation levels in the injury group (p < 0.05). After blocking CCR10 expression in damaged HDMECs by BI6901 (a CCR10 specific blocker) m6A methylation, cell activity, vascular endothelial growth factor A (VEGFA) and CD31 protein expression, as well as relative length and branches of tube formation were found to be increased compared with the injury group, while the levels of inflammatory factors interleukin-1 (IL-1), interleukin-1 (IL-6) and tumor necrosis factor-α (TNF-α) were decreased (p < 0.05).
Conclusions:
Blocking CCR10 expression can activate m6A methylation, promote cell activity, inhibit inflammatory reactions and alleviate HDMEC injury, which may become a breakthrough in future diagnosis and treatment of cardiovascular diseases.
