MiR-539-5p inhibits the inflammatory injury in septic H9c2 cells by regulating IRAK3

Abstract

Background MicroRNAs (miRNAs) have been confirmed to play a potential role in sepsis, but little is known about their role in sepsis-induced cardiomyopathy (SIC). Methods The model of septic cardiomyopathy was constructed with H9c2 cells induced by lipopolysaccharide (LPS), and the expression of miR-539-5p was detected by qRT-PCR assay. ELISA, CCK-8, EdU TUNEL analysis were performed to evaluate the role of miR-539-5p in inflammation response, viability, proliferation and apoptosis of LPS-treated H9c2 cells. Moreover, miRWalk and TargetScan prediction, and dual-luciferase reporter gene assays were carried out to predict and confirm the target of miR-539-5p. Furthermore, the effects of target on inflammation response, proliferation and apoptosis of LPS-induced H9c2 cells mediated by miR-539-5p was further explored. Results The expression of miR-539-5p was obviously down-regulated in LPS-induced H9c2 cells. In addition, over-expression of miR-539-5p significantly inhibited the inflammation response, promoted viability and proliferation, and suppressed apoptosis of LPS-treated H9c2 cells. Moreover, interleukin-1 receptor-associated kinase 3 (IRAK3) was verified as a target of miR-539-5p by dual-luciferase reporter gene assay. Besides, IRAK3 was highly expressed in H9c2 cells transfected with miR-539-5p inhibitor detected with qRT-PCR and western blot assays. Furthermore, over-expression of IRAK3 partially weakened the effects of miR-539-5p mimic on the inflammation response, proliferation and apoptosis of LPS-induced H9c2 cells. Conclusions MiR-539-5p potentially plays an important role in the pathogenesis of LPS-induced sepsis by targeting IRAK3, suggesting that miR-539-5p may be a potential new target for the treatment of LPS-induced sepsis.

miR-484: A Potential Biomarker in Health and Disease

“…In addition, miRNAs have been shown to play a potential role in the pathophysiology and clinical diagnosis and even prognosis of SCI. For example, miR-539-5p targets IRAK3 to inhibit inflammatory release to alleviate LPS-induced sepsis ( 89 ). miR-223 knockout mice significantly exacerbated SIC-induced cardiac dysfunction ( 90 ).…”

Deciphering the molecular classification of pediatric sepsis: integrating WGCNA and machine learning-based classification with immune signatures for the development of an advanced diagnostic model

“…Meta-analyses of in vivo studies substantiate the roles of IRAK3 during the immunosuppression phase of sepsis ( Nguyen et al, 2020 ; Nguyen et al, 2022b ). Notably, miR-539-5p exhibits potential significance in the pathogenesis of LPS-induced sepsis by selectively targeting IRAK3 , suggesting its potential as a therapeutic target for treating LPS-induced sepsis ( Hu and Miao, 2022 ). SESN2 , a stress-inducible protein known as sestrin 2, plays a pivotal role in cellular stress responses and inflammation regulation.…”

IRAK-M deficiency exacerbates dopaminergic neuronal damage in a mouse model of sub-acute Parkinson’s disease

“…IRAK-M prevents the dissociation of IRAK-1 and IRAK-4 from MyD88 and inhibits the formation of IRAK-TRAF6 complexes, and subsequent IκB degradation and NF-κB nuclear translocation [30]. Recent studies from our team and other groups have highlighted their critical role in autoimmune and inflammation-related diseases [12,15,21,[31][32][33]. Herein, IRAK-M was also found to alleviate dopaminergic neuronal injury and inflammatory response and improve behavior in the sub-acute Parkinson's disease model, extending the key role of IRAK-M in central nervous system diseases.…”