ADAR1 Suppresses the Activation of Cytosolic RNA-Sensing Signaling Pathways to Protect the Liver from Ischemia/Reperfusion Injury

作者：Wang, Hui; Wang, Guoliang; Zhang, Liyong; Zhang, Junbin; Zhang, Jinxiang; Wang, Qingde^*; Billiar, Timothy R.^*

来源：Scientific Reports, 2016, 6(1): 20248.

DOI：10.1038/srep20248

• ADENOSINE-DEAMINASE ADAR1
• ISCHEMIA-REPERFUSION INJURY
• I IFN
• INTERFERON
• GENE
• ROLES
• RECOGNITION
• DEFICIENCY
• INDUCTION
• ALPHA

Excessive inflammation resulting from activation of the innate immune system significantly contributes to ischemia/reperfusion injury (IRI). Inflammatory reactions in both IRI and infections share the same signaling pathways evoked by danger/pathogen associated molecular pattern molecules. The cytosolic retinoid-inducible gene I(RIG-I)-like RNA receptor (RLR) RNA sensing pathway mediates type I IFN production during viral infection and the sensing of viral RNA is regulated by adenosine deaminase acting on RNA 1 (ADAR1). Using a model of liver IRI, we provide evidence that ADAR1 also regulates cytosolic RNA-sensing pathways in the setting of ischemic stress. Suppression of ADAR1 significantly enhanced inflammation and liver damage following IRI, which was accompanied by significant increases in type I IFN through cytosolic RNA-sensing pathways. In addition, knocking ADAR1 down in hepatocytes exaggerates inflammatory signaling to dsRNA or endotoxin and results in over production of type I IFN, which could be abolished by the interruption of RIG-I. Therefore, we identified a novel ADAR1-dependent protective contribution through which hepatocytes guard against aberrant cytosolic RLR-RNA-sensing pathway mediated inflammatory reaction in response to acute liver IR. ADAR1 protects against over activation of viral RNA-sensing pathways in non-infectious tissue stress.

• 出版日期2016-2-1
• 单位华中科技大学; 中南大学