MicroR-380-3p Reduces Sepsis-Induced Acute Kidney Injury via Regulating RAB1P to Restrain NF-κB Pathway

MicroR-380-3p Reduces Sepsis-Induced Acute Kidney Injury via Regulating RAB1P to Restrain NF-κB Pathway

Jifang Liang,^1,2 Bo Li¹ and Yanmei Xia^1,2

¹Department of Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
²Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

Septic acute kidney injury (AKI) is a common complication in critically ill patients with high morbidity and mortality. This study intends to clarify the clinical value and molecular mechanism of microR-380-3p in septic AKI by recruiting patients with septic AKI and establishing septic AKI cell models. Patients with septic AKI were included and human kidney-2 (HK-2) cells were induced by lipopolysaccharide (LPS) to construct the AKI cell model of sepsis. The expression of microR-380-3p was detected by quantitative real-time RT-PCR (qRT-PCR). The expression of Bax, cleaved caspase 3, Bcl-2, p65, and p-p65 was detected by Western blot. The contents of inflammation and oxidation were determined by commercial kits. Bioinformatics predicted the binding target of microR-380-3p and a dual luciferase reporting system was used to verify the regulatory relationship between microR-380-3p and RAP1B. The concentration of microR-380-3p was elevated in patients with septic AKI and appeared to be a biomarker for these patients. Silenced microR-380-3p reversed the damage of LPS on HK-2 cells via promoting viability, inhibiting apoptosis, inflammation, and oxidation. RAP1B was a target of microR-380-3p and microR-380-3p exerted targeted inhibition of RAP1B expression level. Down-regulation of RAP1B reversed the influence of silenced microR-380-3p on HK-2 cells. MicroR-380-3p/RAP1B participated in activating the NF-κB pathway. MicroR-380-3p down-regulated RAP1B to exacerbate septic AKI, providing a potential therapeutic biomarker for septic AKI.

Key words —— diagnostic value; microR-380-3p; NF-κB pathway; RAP1B; septic AKI

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Tohoku J. Exp. Med., 2024 May, 263(1), 69-79.

Correspondence: Yanmei Xia, Department of Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, No. 99, Longcheng Street Xiaodian District, Taiyuan, Shanxi 030032, China.

Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.

e-mail: xiayanmeidr@163.com