Matches in SemOpenAlex for { <https://semopenalex.org/work/W4249595890> ?p ?o ?g. }
Showing items 1 to 65 of
65
with 100 items per page.
- W4249595890 abstract "Abstract Background Pathological stimuli cause mitochondrial damage and leakage of mitochondrial DNA (mtDNA) into the cytosol, as demonstrated in many cell types. The cytosolic mtDNA then drives the activation of noninfectious inflammation. Retinal microvascular endothelial cells (RMECs) play an important role in the inner endothelial blood–retinal barrier (BRB). RMEC dysfunction frequently occurs in posterior-segment eye diseases, causing loss of vision. In this study, we investigated the involvement of cytosolic mtDNA in noninfectious immune inflammation in RMECs under pathological stimuli.Methods RMECs were stimulated with 100 ng/ml lipopolysaccharide (LPS), 200 μM hydrogen peroxide (H 2 O 2 ), or 25 mM d -glucose. After 24 h, immunofluorescent staining was used to detect the opening of the mitochondrial permeability transition pore (MPTP). Cytosolic mtDNA was detected with immunofluorescent staining and PCR after stimulation. mtDNA was then isolated and used to transfect RMECs in vitro, and the protein levels of cGAS were evaluated with western blotting. Real-time PCR was used to examine cGAS mRNA expression levels at different time points after mtDNA stimulation. The activation of STING was detected with immunofluorescent staining 6 h after mtDNA stimulation. Western blotting was used to determine the phosphorylation status of TBK1, IRF3, and nuclear factor-κB (NF-κB) P65, and the nuclear translocation of IRF3 and NF-κB P65 at 0, 3, 6, 12, and 24 h. The mRNA expression of proinflammatory cytokines CCL4, CXCL10, IRF1, and IFNB1 was determined with real-time PCR, together with the concentrations of intercellular adhesion molecule 1 (ICAM-1) mRNA.Results Pathological stimuli caused mtDNA to leak into the cytosol by opening the MPTP in RMECs after 24 h. Cytosolic mtDNA regulated the expression of cGAS and the distribution of STING in RMECs. It promoted TBK1, IRF3, and NF-κB phosphorylation and the nuclear translocation in RMECs at 12 and 24 h after its transfection. The mRNAs of proinflammatory cytokines CCL4, CXCL10, IRF1, and IFNB1 were significantly elevated at 12 and 24 h after mtDNA stimulation.Conclusions Pathological stimulation induces mtDNA escape into the cytosol of RMECs. This cytoplasmic mtDNA is recognized by the DNA sensor cGAS, increasing the expression of inflammatory cytokines through the STING–TBK1 signaling pathway." @default.
- W4249595890 created "2022-05-12" @default.
- W4249595890 creator A5014653261 @default.
- W4249595890 creator A5022010854 @default.
- W4249595890 creator A5039418486 @default.
- W4249595890 creator A5074942308 @default.
- W4249595890 creator A5083376773 @default.
- W4249595890 creator A5086098476 @default.
- W4249595890 date "2020-03-04" @default.
- W4249595890 modified "2023-10-17" @default.
- W4249595890 title "Mitochondrial DNA drives noncanonical inflammation activation via cGAS–STING signaling pathway in retinal microvascular endothelial cells" @default.
- W4249595890 doi "https://doi.org/10.21203/rs.3.rs-16034/v1" @default.
- W4249595890 hasPublicationYear "2020" @default.
- W4249595890 type Work @default.
- W4249595890 citedByCount "0" @default.
- W4249595890 crossrefType "posted-content" @default.
- W4249595890 hasAuthorship W4249595890A5014653261 @default.
- W4249595890 hasAuthorship W4249595890A5022010854 @default.
- W4249595890 hasAuthorship W4249595890A5039418486 @default.
- W4249595890 hasAuthorship W4249595890A5074942308 @default.
- W4249595890 hasAuthorship W4249595890A5083376773 @default.
- W4249595890 hasAuthorship W4249595890A5086098476 @default.
- W4249595890 hasBestOaLocation W42495958901 @default.
- W4249595890 hasConcept C104317684 @default.
- W4249595890 hasConcept C13591479 @default.
- W4249595890 hasConcept C153911025 @default.
- W4249595890 hasConcept C164027704 @default.
- W4249595890 hasConcept C190283241 @default.
- W4249595890 hasConcept C203014093 @default.
- W4249595890 hasConcept C2776914184 @default.
- W4249595890 hasConcept C31573885 @default.
- W4249595890 hasConcept C55493867 @default.
- W4249595890 hasConcept C85265743 @default.
- W4249595890 hasConcept C86803240 @default.
- W4249595890 hasConcept C95444343 @default.
- W4249595890 hasConceptScore W4249595890C104317684 @default.
- W4249595890 hasConceptScore W4249595890C13591479 @default.
- W4249595890 hasConceptScore W4249595890C153911025 @default.
- W4249595890 hasConceptScore W4249595890C164027704 @default.
- W4249595890 hasConceptScore W4249595890C190283241 @default.
- W4249595890 hasConceptScore W4249595890C203014093 @default.
- W4249595890 hasConceptScore W4249595890C2776914184 @default.
- W4249595890 hasConceptScore W4249595890C31573885 @default.
- W4249595890 hasConceptScore W4249595890C55493867 @default.
- W4249595890 hasConceptScore W4249595890C85265743 @default.
- W4249595890 hasConceptScore W4249595890C86803240 @default.
- W4249595890 hasConceptScore W4249595890C95444343 @default.
- W4249595890 hasLocation W42495958901 @default.
- W4249595890 hasLocation W42495958902 @default.
- W4249595890 hasLocation W42495958903 @default.
- W4249595890 hasOpenAccess W4249595890 @default.
- W4249595890 hasPrimaryLocation W42495958901 @default.
- W4249595890 hasRelatedWork W14071738 @default.
- W4249595890 hasRelatedWork W19695552 @default.
- W4249595890 hasRelatedWork W20102366 @default.
- W4249595890 hasRelatedWork W33150249 @default.
- W4249595890 hasRelatedWork W35595014 @default.
- W4249595890 hasRelatedWork W37687275 @default.
- W4249595890 hasRelatedWork W40112019 @default.
- W4249595890 hasRelatedWork W4209463 @default.
- W4249595890 hasRelatedWork W4338933 @default.
- W4249595890 hasRelatedWork W8535622 @default.
- W4249595890 isParatext "false" @default.
- W4249595890 isRetracted "false" @default.
- W4249595890 workType "article" @default.