Item request has been placed!
×
Item request cannot be made.
×
![loading](/sites/all/modules/hf_eds/images/loading.gif)
Processing Request
Mitochondrial DNA release via the mitochondrial permeability transition pore activates the cGAS-STING pathway, exacerbating inflammation in acute Kawasaki disease.
Item request has been placed!
×
Item request cannot be made.
×
![loading](/sites/all/modules/hf_eds/images/loading.gif)
Processing Request
- معلومة اضافية
- المصدر:
Publisher: BioMed Central Country of Publication: England NLM ID: 101170464 Publication Model: Electronic Cited Medium: Internet ISSN: 1478-811X (Electronic) Linking ISSN: 1478811X NLM ISO Abbreviation: Cell Commun Signal Subsets: MEDLINE
- بيانات النشر:
Original Publication: [London] : BioMed Central, c2003-
- الموضوع:
- نبذة مختصرة :
Background: Kawasaki disease (KD) is an immune vasculitis of unknown origin, characterized by transient inflammation. The activation of the cGAS-STING pathway, triggered by mitochondrial DNA (mtDNA) release, has been implicated in the onset of KD. However, its specific role in the progression of inflammation during KD's acute phase remains unclear.
Methods: We measured mtDNA and 2'3'-cGAMP expression in KD patient serum using RT-qPCR and ELISA. A murine model of KD was induced by injecting Lactobacillus casei cell wall extract (LCWE), after which cGAS-STING pathway activation and inflammatory markers were assessed via immunohistochemistry, western blot, and RT-qPCR. Human umbilical vein endothelial cells (HUVECs) were treated with KD serum and modulators of the cGAS-STING pathway for comparative analysis. Mitochondrial function was evaluated using Mitosox staining, mPTP opening was quantified by fluorescence microscopy, and mitochondrial membrane potential (MMP) was determined with JC-1 staining.
Results: KD patient serum exhibited increased mtDNA and 2'3'-cGAMP expression, with elevated levels of pathway-related proteins and inflammatory markers observed in both in vivo and in vitro models. TEM confirmed mitochondrial damage, and further studies demonstrated that inhibition of mPTP opening reduced mtDNA release, abrogated cGAS-STING pathway activation, and mitigated inflammation.
Conclusion: These findings indicate that mtDNA released through the mPTP is a critical activator of the cGAS-STING pathway, contributing significantly to KD-associated inflammation. Targeting mtDNA release or the cGAS-STING pathway may offer novel therapeutic approaches for KD management.
(© 2024. The Author(s).)
- References:
Circulation. 2018 Jun 12;137(24):2613-2634. (PMID: 29437120)
Nat Rev Immunol. 2021 Sep;21(9):548-569. (PMID: 33833439)
Front Immunol. 2022 Oct 10;13:1017401. (PMID: 36300112)
JCI Insight. 2021 Sep 22;6(18):. (PMID: 34403365)
Chin Med J (Engl). 2024 May 5;137(9):1044-1053. (PMID: 38445370)
Cells. 2021 Oct 26;10(11):. (PMID: 34831121)
Nat Commun. 2019 May 21;10(1):2261. (PMID: 31113940)
Br J Pharmacol. 2012 Mar;165(5):1235-45. (PMID: 21955136)
Circulation. 2020 Jan 7;141(1):42-66. (PMID: 31887080)
Birth Defects Orig Artic Ser. 1975;11(2):344-6. (PMID: 132203)
Invest Ophthalmol Vis Sci. 2024 Apr 1;65(4):33. (PMID: 38648040)
Biochem Soc Trans. 2023 Feb 27;51(1):457-472. (PMID: 36815695)
Front Immunol. 2020 Apr 28;11:615. (PMID: 32411126)
Arthritis Rheum. 1985 Jun;28(6):652-9. (PMID: 3924060)
Ann Rheum Dis. 2018 Oct;77(10):1507-1515. (PMID: 29945921)
Cell Commun Signal. 2020 Oct 28;18(1):172. (PMID: 33115500)
Circ Res. 2023 May 26;132(11):e223-e242. (PMID: 37154056)
Cell Commun Signal. 2021 May 20;19(1):58. (PMID: 34016129)
Biochem Biophys Res Commun. 2023 Feb 12;644:15-24. (PMID: 36621148)
Microbiol Immunol. 1979;23(9):825-31. (PMID: 395420)
Front Immunol. 2022 Jan 27;13:790095. (PMID: 35154107)
Circulation. 2019 Jul 30;140(5):e181-e184. (PMID: 31356128)
Theranostics. 2021 Jan 1;11(4):1845-1863. (PMID: 33408785)
Mol Cell. 2022 Mar 3;82(5):933-949.e9. (PMID: 35120587)
Molecules. 2020 Jun 21;25(12):. (PMID: 32575813)
Exp Mol Med. 2023 Mar;55(3):510-519. (PMID: 36964253)
Biol Rev Camb Philos Soc. 2017 Aug;92(3):1459-1474. (PMID: 27455896)
J Mol Cell Cardiol. 2009 Jun;46(6):821-31. (PMID: 19265700)
Cell Death Discov. 2022 May 11;8(1):258. (PMID: 35538059)
Int Immunopharmacol. 2019 Nov;76:105791. (PMID: 31472320)
Exp Mol Med. 2022 Feb;54(2):129-142. (PMID: 35145201)
Clin Transl Immunology. 2021 May 10;10(5):e1284. (PMID: 33981434)
Immunity. 2022 Aug 9;55(8):1370-1385.e8. (PMID: 35835107)
Biomed Pharmacother. 2020 May;125:110022. (PMID: 32106379)
Arthritis Care Res (Hoboken). 2022 Apr;74(4):538-548. (PMID: 35257507)
Immunity. 2021 May 11;54(5):962-975.e8. (PMID: 33857420)
Ann Med. 2018 Mar;50(2):121-127. (PMID: 29237304)
Mol Ther. 2022 Nov 2;30(11):3477-3498. (PMID: 35791879)
J Appl Toxicol. 2024 Mar 11;:. (PMID: 38462915)
Methods Mol Biol. 2012;810:183-205. (PMID: 22057568)
Cells. 2019 Apr 25;8(4):. (PMID: 31027297)
Clin Exp Immunol. 2020 Mar;199(3):303-313. (PMID: 31758701)
Exp Cell Res. 2021 Dec 15;409(2):112941. (PMID: 34822812)
Ann Intensive Care. 2011 Sep 26;1(1):41. (PMID: 21942988)
- Grant Information:
SJCX23_1802 Graduate Practice Innovation Program of Jiangsu Province; SYH-32034-0082 Jiangsu Provincial Medical Association; 82270528 National Natural Science Foundation of China; ZDA2020010 Jiangsu Provincial Commission of Health and Family Planning; MS22022116 People's Livelihood Science and Technology Projetct of Nantong Science and Technology Bureau; F202154 Maternal and Child Health Project of Jiangsu Provincial Health Commission; LCYJ-A06 Multi-centre Clinical Collaborative Research Project at Affiliated Hospital of Nantong University; NTCXTD43 Nantong Municipal Health Commission 14th Five-Year Plan Innovation Team
- Contributed Indexing:
Keywords: Kawasaki disease; cGAS-STING pathway; mPTP; mtDNA
- الرقم المعرف:
0 (DNA, Mitochondrial)
EC 2.7.7.- (Nucleotidyltransferases)
0 (Membrane Proteins)
0 (Mitochondrial Permeability Transition Pore)
0 (STING1 protein, human)
EC 2.7.7.- (cGAS protein, human)
- الموضوع:
Date Created: 20240613 Date Completed: 20240614 Latest Revision: 20240626
- الموضوع:
20240626
- الرقم المعرف:
PMC11177463
- الرقم المعرف:
10.1186/s12964-024-01677-9
- الرقم المعرف:
38872145
No Comments.