MicroRNA-30a inhibits cell proliferation in a sepsis-induced acute kidney injury model by targeting the YAP-TEAD complex  

作　　者：Junfeng Su Ying Wang Jing Xie Long Chen Xinxin Lin Jiandong Lin Xiongjian Xiao 

机构地区：[1]Department of General Intensive Care Unit,The Second Affiliated Hospital of Zhejiang University School of Medicine,Hangzhou,China [2]Department of Critical Care Medicine,The First Affiliated Hospital,Fujian Medical University,Fuzhou,China [3]Department of Critical Care Medicine,National Regional Medical Center,Binhai Campus of the First Affiliated Hospital,Fujian Medical University,Fuzhou,China

出　　处：《Journal of Intensive Medicine》2024年第2期231-239,共9页重症医学（英文）

摘　　要：Background Acute kidney injury(AKI)is a primary feature of renal complications in patients with sepsis.MicroRNA(miRNA/miR)-30a is an essential regulator of cardiovascular diseases,tumors,phagocytosis,and other physical processes,but whether it participates in sepsis-induced AKI(sepsis-AKI)is unknown.We aimed to elucidate the functions and molecular mechanism underlying miR-30a activity in sepsis-AKI.Methods The classical cecal ligation and puncture(CLP)method and lipopolysaccharide(LPS)-induced Human Kidney 2(HK-2)cells were used to establish in vivo and in vitro sepsis-AKI models.Specific pathogen-free and mature male Sprague-Dawley(SD)rats,aged 6–8 weeks(weight 200–250 g),were randomly divided into five-time phase subgroups.Fluid resuscitation with 30 mL/kg 37°C saline was administered after the operation,without antibiotics.Formalin-fixed,paraffin-embedded kidney sections were stained with hematoxylin and eosin.SD rat kidney tissue samples were collected for analysis by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay.HK-2 cells were transfected with hsa-miR-30a-3p mimics or inhibitors,and compared with untreated normal controls.RNA,protein,and cell viability were evaluated by quantitative reverse transcription-polymerase chain reaction(qRT-PCR),western blot,and cell counting kit-8 methods.A Dual-Luciferase Assay Kit(Promega)was used to measure luciferase activity 48 h after transfection with miR-30a-3p mimics.Results Expression levels of miR-30a-3p and miR-30a-5p in renal tissues of the sepsis group were significantly reduced at 12 h and 24 h(P<0.05).Tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were significantly increased in renal tissue 3 h after the operation in rats(P<0.05),and gradually decreased 6 h,12 h,and 24 h after CLP.Levels of miR-30a-5p and miR-30a-3p were significantly down-regulated at 3 h after LPS treatment(P<0.05),and gradually decreased in HK-2 cells.One hour after LPS(10µg/mL)treatment,TNF-αand IL-1βlevels in HK-2 cells were signi

关 键 词：MicroRNA-30a TEAD1 YAP-TEAD complex SEPSIS Acute kidney injury 

分 类 号：R692[医药卫生—泌尿科学] R459.7[医药卫生—外科学]