miR-155 induces sepsis-associated damage to the intestinal mucosal barrier via sirtuin 1/nuclear factor-κB-mediated intestinal pyroptosis  

作　　者：Zhihua Li Yi Wang Weiwei Huang Xingyu Shi Tao Ma Xiangyou Yu 

机构地区：[1]The First Affiliated Hospital of Xinjiang Medical University,Urumqi,Xinjiang 830054,China [2]Department of Critical Medicine,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第11期1618-1632,共15页生物化学与生物物理学报(英文版)

基　　金：This work was supported by the grant from the National Natural Science Foundation of China(No.82160360).

摘　　要：Sepsis is a life-threatening state of organ dysfunction caused by systemic inflammation and a dysfunctional response to host infections that can induce severe intestinal mucosal damage.Pyroptosis is mediated by the activated NOD-like receptor family pyrin domain-containing 3(NLRP3)inflammasome after stimulation by various inflammatory factors during sepsis.The inflammatory response is a major driver of intestinal damage during sepsis.Intestinal mucosal barrier dysfunction in sepsis is associated with pyroptosis,a type of programmed inflammatory cell death.Several studies have confirmed the role of miR-155 in sepsis and other diseases.However,the effect of miR-155 on intestinal pyroptosis in the context of intestinal mucosal barrier dysfunction during sepsis remains unclear.Thus,a model of sepsis in Sprague-Dawley rats is established using cecal ligation and puncture(CLP),and a series of molecular biological methods are used in this study.The results show that the expression of miR-155 is increased and that of sirtuin 1(SIRT1)is decreased in the intestinal tissues of patients with sepsis.miR-155 expression is negatively correlated with SIRT1 expression.Increased miR-155 expression significantly inhibits SIRT1 activity and upregulates the expressions of NOD-like receptor family pyrin domain-containing 3(NLRP3),caspase-1,apoptosis-associated speck-like protein containing a CARD(ASC),interleukin-1β(IL-1β)and interleukin-18(IL-18)to promote pyroptosis.The inhibition of miR-155 expression is associated with increased SIRT1 expression,promotes the deacetylation of p65,and significantly downregulates p65 acetylation.Herein,we propose that miR-155 induces pyroptosis in the intestine partly by regulating SIRT1,thereby reducing the deacetylation of the nuclear factor(NF)-κB subunit p65 and increasing NF-κB signaling activity in sepsis,leading to intestinal barrier damage.

关 键 词：intestinal barrier dysfunction MIR-155 NF-KB PYROPTOSIS SEPSIS SIRT1 

分 类 号：R574[医药卫生—消化系统]