Back to Search
Start Over
cGAS-mediated autophagy protects the liver from ischemia-reperfusion injury independently of STING.
- Source :
-
American Journal of Physiology: Gastrointestinal & Liver Physiology . Jun2018, Vol. 314 Issue 6, pG655-G667. 13p. - Publication Year :
- 2018
-
Abstract
- Liver ischemia-reperfusion (I/R) injury occurs through induction of oxidative stress and release of damage-associated molecular patterns (DAMPs), including cytosolic DNA released from dysfunctional mitochondria or from the nucleus. Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) is a cytosolic DNA sensor known to trigger stimulator of interferon genes (STING) and downstream type 1 interferon (IFN-I) pathways, which are pivotal innate immune system responses to pathogen. However, little is known about the role of cGAS/STING in liver I/R injury. We subjected C57BL/6 (WT), cGAS knockout (cGAS-/-), and STING-deficient (STINGgt/gt) mice to warm liver I/R injury and that found cGAS-/- mice had significantly increased liver injury compared with WT or STINGgt/gt mice, suggesting a protective effect of cGAS independent of STING. Liver I/R upregulated cGAS in vivo and also in vitro in hepatocytes subjected to anoxia/reoxygenation (A/R). We confirmed a previously published finding that hepatocytes do not express STING under normoxic conditions or after A/R. Hepatocytes and liver from cGAS-/- mice had increased cell death and reduced induction of autophagy under hypoxic conditions as well as increased apoptosis. Protection could be restored in cGAS-/- hepatocytes by overexpression of cGAS or by pretreatment of mice with autophagy inducer rapamycin. Our findings indicate a novel protective role for cGAS in the regulation of autophagy during liver I/R injury that occurs independently of STING. [ABSTRACT FROM AUTHOR]
- Subjects :
- *GUANYLIC acid
*ISCHEMIA
*REPERFUSION injury
Subjects
Details
- Language :
- English
- ISSN :
- 01931857
- Volume :
- 314
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- American Journal of Physiology: Gastrointestinal & Liver Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 130003388
- Full Text :
- https://doi.org/10.1152/ajpgi.00326.2017