AUTHOR=Wang Xincai , Huang Long , Xu Jingqing , Li Min , Zhang Hongxuan , Yao Yuqing , Liu Yaqing , Lin Xingsheng , Shang Xiuling 

TITLE=MicroRNA-27b alleviates septic cardiomyopathy by targeting the Mff/MAVS axis

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 15 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1588461

DOI=10.3389/fcimb.2025.1588461

ISSN=2235-2988

ABSTRACT=ObjectiveTo investigate the protective role of microRNA-27b (miR-27b) in septic cardiomyopathy (SCM) and its regulatory mechanism on the mitochondrial fission factor (Mff)/mitochondrial antiviral signaling protein (MAVS) axis.MethodsTranscriptome data from septic patients’ cardiac tissues (GSE79962) were analyzed. Serum miR-27b expression was measured in SCM patients (n=11), sepsis-only patients (n=22), and healthy controls (n=30). Mouse SCM model and HL-1 cardiomyocyte model were established by lipopolysaccharide (LPS) induction. The molecular mechanism was investigated using miR-27b agonist/antagonist and Mff intervention, combined with RT-qPCR, Western blot, immunofluorescence, and transmission electron microscopy.ResultsBioinformatics analysis revealed significant downregulation of miR-27b in SCM cardiac tissues (log2FC=-3.9, P<0.001). Clinical validation showed lower miR-27b expression in SCM patients’ serum compared to sepsis-only patients and healthy controls (P<0.05). LPS-induced SCM model exhibited cardiac dysfunction, myocardial injury, mitochondrial abnormalities, decreased miR-27b expression, and increased Mff and MAVS levels. miR-27b targeted Mff to maintain mitochondrial homeostasis, thus attenuating LPS-induced cardiomyocyte inflammation and apoptosis, while Mff overexpression reversed this protective effect.ConclusionmiR-27b alleviates myocardial injury and inflammation in SCM by targeting the Mff/MAVS axis to maintain mitochondrial homeostasis, representing a potential novel therapeutic target for SCM.