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Double-stranded RNA orbivirus disrupts the DNA-sensing cGAS-sting axis to prevent type I IFN induction.
Cell Mol Life Sci
January 2025
Centro de Investigación en Sanidad Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Científicas (CISA-INIA-CSIC), Valdeolmos, Madrid, Spain.
Cyclic GMP-AMP synthase (cGAS) is a DNA sensing cellular receptor that induces IFN-I transcription in response to pathogen and host derived cytosolic DNA and can limit the replication of some RNA viruses. Some viruses have nonetheless evolved mechanisms to antagonize cGAS sensing. In this study, we evaluated the interaction between Bluetongue virus (BTV), the prototypical dsRNA virus of the Orbivirus genus and the Sedoreoviridae family, and cGAS.
View Article and Find Full Text PDFcGAS-STING signaling pathway in lung cancer: Regulation on antitumor immunity and application in immunotherapy.
Chin Med J Pulm Crit Care Med
December 2024
Department of Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai 200433, China.
The innate immune system has a primary role in defending against external threats, encompassing viruses, bacteria, and fungi, thereby playing a pivotal role in establishing robust protection. Recent investigations have shed light on its importance in the progression of tumors, with a particular emphasis on lung cancer. Among the various signaling pathways implicated in this intricate process, the cGAS-STING pathway emerges as a significant participant.
View Article and Find Full Text PDFThis study investigates the synergistic inhibitory effects of combining the stimulator of interferon genes (STING) agonist cyclic diadenylate monophosphate (c-di-AMP) and ginsenoside RG3 on cisplatin (DDP)-resistant gastric cancer (GC) cells. The objective is to identify novel therapeutic targets and offers insights for the clinical management of DDP resistance. Various techniques were employed, including western blot, MTT assay, colony formation assay, scratch assay, transwell assay, tubule formation assay, flow cytometry, Hoechst 33342 fluorescence staining, and in vivo experiments, to investigate the potential mechanisms and effects of the combined application of the STING agonist and ginsenoside RG3 in reversing cisplatin resistance in gastric cancer.
View Article and Find Full Text PDFGenetic deficiency or pharmacological inhibition of cGAS-STING signalling suppresses kidney inflammation and fibrosis.
Br J Pharmacol
January 2025
Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut, USA.
Background And Purpose: Chronic kidney disease (CKD) is characterised by inflammation, which can lead to tubular atrophy and fibrosis. The molecular mechanisms are not well understood. In this study, we investigated the functional role of the cyclic GMP-AMP synthase (cGAS)- stimulator of interferon genes (STING) signalling in renal inflammation and fibrosis.
View Article and Find Full Text PDFMicroglial double stranded DNA accumulation induced by DNase II deficiency drives neuroinflammation and neurodegeneration.
J Neuroinflammation
January 2025
State Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Haidian District, Beijing, 100190, China.
Background: Deoxyribonuclease 2 (DNase II) is pivotal in the clearance of cytoplasmic double stranded DNA (dsDNA). Its deficiency incurs DNA accumulation in cytoplasm, which is a hallmark of multiple neurodegenerative diseases. Our previous study showed that neuronal DNase II deficiency drove tau hyperphosphorylation and neurodegeneration (Li et al.
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