MicroRNA-23a reduces lipopolysaccharide-induced cellular apoptosis and inflammatory cytokine production through Rho-associated kinase 1/sirtuin-1/nuclear factor-kappa B crosstalk

Abstract

Background: MicroRNAs are closely associated with the progression and outcomes of multiple human diseases, including sepsis. In this study, we examined the role of miR-23a in septic injury. Methods: Lipopolysaccharide (LPS) was used to induce sepsis in a rat model and H9C2 and HK-2 cells. miR-23a expression was evaluated in rat myocardial and kidney tissues, as well as H9C2 and HK-2 cells. A miR-23a mimic was introduced into cells to identify the role of miR-23a in cell viability, apoptosis, and the secretion of inflammatory cytokines. Furthermore, the effect of Rho-associated kinase 1 ( ROCK1 ), a miR-23a target, on cell damage was evaluated, and molecules involved in the underlying mechanism were identified. Results: In the rat model, miR-23a was poorly expressed in myocardial (sham vs . sepsis 1.00 ± 0.06 vs. 0.27 ± 0.03, P < 0.01) and kidney tissues (sham vs. sepsis 0.27 ± 0.03 vs. 1.00 ± 0.06, P < 0.01). Artificial overexpression of miR-23a resulted in increased proliferative activity (DNA replication rate: Control vs. LPS vs. LPS + Mock vs. LPS + miR-23a: H9C2 cells: 34.13 ± 3.12 vs. 12.94 ± 1.21 vs. 13.31 ± 1.43 vs. 22.94 ± 2.26, P < 0.05; HK-2 cells: 15.17 ± 1.43 vs. 34.52 ± 3.46 vs. 35.19 ± 3.12 vs. 19.87 ± 1.52, P < 0.05), decreased cell apoptosis (Control vs. LPS vs. LPS + Mock vs. LPS + miR-23a: H9C2 cells: 11.39 ± 1.04 vs. 32.57 ± 2.29 vs. 33.08 ± 3.12 vs. 21.63 ± 2.35, P < 0.05; HK-2 cells: 15.17 ± 1.43 vs. 34.52 ± 3.46 vs. 35.19 ± 3.12 vs. 19.87 ± 1.52, P < 0.05), and decreased production of inflammatory cytokines, including interleukin-6 (Control vs. LPS vs. LPS + Mock vs. LPS + miR-23a: H9C2 cells: 59.61 ± 5.14 vs. 113.54 ± 12.30 vs. 116.51 ± 10.69 vs. 87.69 ± 2.97 ng/mL; P < 0.05, F = 12.67, HK-2 cells: 68.12 ± 6.44 vs. 139.65 ± 16.62 vs. 143.51 ± 13.64 vs. 100.82 ± 9.74 ng/mL, P < 0.05, F ...

Research Progress on the Mechanism of Sepsis Induced Myocardial Injury

“…Similarly, miR-23a suppressed sepsis-induced inflammatory responses by inhibiting the SIRT1/NF-κB signaling pathway as well. 134 The inflammatory storm of cardiomyocytes in sepsis may be also caused by inhibition of phosphorylation of AMPK signaling pathway. 135 The Role of Genomics in Over-Inflammation…”

Potential of Polyphenols to Restore SIRT1 and NAD+ Metabolism in Renal Disease

“…For example, during lipopolysaccharide (LPS)-induced kidney injury, the miR-23 was reduced and associated with an increase in Rho-associated kinase 1 (ROCK1). ROCK1 suppressed SIRT1, leading to the activation of NFκB [ 96 ].…”

Downregulation of microRNA-23a confers protection against myocardial ischemia/reperfusion injury by upregulating tissue factor pathway inhibitor 2 following luteolin pretreatment in rats

“…MiRNAs are potential therapeutic targets in various diseases. [ 4 ] Eight miRNAs (miRNA-1, -21, -23a, -24, -133a, -199a-3p, -214, and -378) were searched for in MEDLINE, PubMed Central, and the Human microRNA Disease Database. The reverse transcription polymerase chain reaction (RT-PCR) results showed that miRNA-1, -23a, -24, -133a, and -378 were upregulated in perfused rat hearts after MI/RI, but that luteolin pretreatment downregulated miRNA-23a and upregulated miR-378.…”

“…MiRNAs are potential therapeutic targets in various diseases [4] . Eight miRNAs (miRNA-1, -21, -23a, -24, -133a, -199a-3p, -214, and -378) were searched for in MEDLINE, PubMed Central, and the Human microRNA Disease Database.…”