Related Experiment Video
Updated: Aug 8, 2025
Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
SILENCING M 6 A READER YTHDC1 REDUCES INFLAMMATORY RESPONSE IN SEPSIS-INDUCED CARDIOMYOPATHY BY INHIBITING SERPINA3N
Wenjing Xie1, Anqi Zhang, Xuliang Huang
1Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Abstract:
Sepsis-induced cardiomyopathy (SIC) is one of the most common complications of infection-induced sepsis. An imbalance in inflammatory mediators is the main factor leading to SIC . N 6 -methyladenosine (m 6 A) is closely related to the occurrence and development of sepsis. N 6 -methyladenosine reader YTH domain containing 1 (YTHDC1) is an m 6 A N 6 -methyladenosine recognition protein. However, the role of YTHDC1 in SIC remains unclear. Herein, we demonstrated that YTHDC1-shRNA inhibits inflammation, reduces inflammatory mediators, and improves cardiac function in a LPS-induced SIC mouse model. Based on the Gene Expression Omnibus database analysis, serine protease inhibitor A3N is a differential gene of SIC. Furthermore, RNA immunoprecipitation indicated that serine protease inhibitor A3N (SERPINA3N) mRNA can bind to YTHDC1, which regulates the expression of SERPINA3N. Serine protease inhibitor A3N-siRNA reduced LPS-induced inflammation of cardiac myocytes. In conclusion, the m 6 A reader YTHDC1 regulates SERPINA3N mRNA expression to mediate the levels of inflammation in SIC. Such findings add to the relationship between m 6 A reader YTHDC1 and SIC, providing a new research avenue for the therapeutic mechanism of SIC.
Insights
The m6A reader YTHDC1 regulates SERPINA3N mRNA, reducing inflammation and improving cardiac function in sepsis-induced cardiomyopathy. This finding offers new therapeutic insights for sepsis complications.
Area of Science:
- Molecular Biology
- Cardiovascular Research
- Immunology
Background:
- Sepsis-induced cardiomyopathy (SIC) is a common sepsis complication driven by inflammatory mediator imbalance.
- N6-methyladenosine (m6A) modification is implicated in sepsis development.
- The role of the m6A reader YTHDC1 in SIC is currently unknown.
Purpose of the Study:
- To investigate the role of YTHDC1 in sepsis-induced cardiomyopathy.
- To explore the regulatory relationship between YTHDC1 and SERPINA3N in SIC.
Main Methods:
- Utilized a lipopolysaccharide (LPS)-induced mouse model of SIC.
- Employed YTHDC1-shRNA and SERPINA3N-siRNA for knockdown experiments.
- Analyzed Gene Expression Omnibus database for differential gene expression.
- Performed RNA immunoprecipitation to confirm mRNA binding.
Main Results:
- YTHDC1 inhibition reduced inflammation and improved cardiac function in an LPS-induced SIC model.
- SERPINA3N was identified as a differentially expressed gene in SIC.
- YTHDC1 directly binds to and regulates SERPINA3N mRNA expression.
- SERPINA3N knockdown decreased LPS-induced inflammation in cardiac myocytes.
Conclusions:
- The m6A reader YTHDC1 plays a crucial role in mediating inflammation in SIC by regulating SERPINA3N.
- These findings establish a link between YTHDC1 and SIC, suggesting YTHDC1 as a potential therapeutic target.
