Send to

Choose Destination
Sci Rep. 2016 Feb 1;6:20248. doi: 10.1038/srep20248.

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

Author information

Department of Medical Genetics, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
F1281 UPMC Presbyterian Hospital, 200 Lothrop St, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15261, USA.
Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.
Third Xiangya Hospital, Central South University, Changsha, China 410083.


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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center