Reference - Detail
| RRC ID | 58937 |
|---|---|
| Author | Maekawa H, Inoue T, Ouchi H, Jao TM, Inoue R, Nishi H, Fujii R, Ishidate F, Tanaka T, Tanaka Y, Hirokawa N, Nangaku M, Inagi R. |
| Title | Mitochondrial Damage Causes Inflammation via cGAS-STING Signaling in Acute Kidney Injury. |
| Journal | Cell Rep |
| Abstract |
Acute kidney injury (AKI) is characterized by mitochondrial dysfunction and activation of the innate immune system. The cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway detects cytosolic DNA and induces innate immunity. Here, we investigate the role of mitochondrial damage and subsequent activation of the cGAS-STING pathway using a genetically engineered animal model of cisplatin-induced AKI and cultured tubular cells. Cisplatin induced mtDNA leakage into the cytosol-probably through BCL-2-like protein 4 (BAX) pores in the mitochondrial outer membrane-in tubules, with subsequent activation of the cGAS-STING pathway, thereby triggering inflammation and AKI progression, which is improved in STING-deficient mice. STING knockdown in cultured tubular cells ameliorates inflammatory responses induced by cisplatin. mtDNA depletion and repletion studies support tubular inflammatory responses via the cGAS-STING signal activation by cytosolic mtDNA. Therefore, we conclude that mitochondrial dysfunction and subsequent activation of the mtDNA-cGAS-STING pathway is a critical regulator of kidney injury. |
| Volume | 29(5) |
| Pages | 1261-1273.e6 |
| Published | 2019-10-29 |
| DOI | 10.1016/j.celrep.2019.09.050 |
| PII | S2211-1247(19)31238-0 |
| PMID | 31665638 |
| MeSH | Acute Kidney Injury / chemically induced Acute Kidney Injury / metabolism* Acute Kidney Injury / pathology* Animals Cell Line Cell Movement / drug effects Cisplatin / adverse effects Cytosol / metabolism DNA, Mitochondrial / metabolism Humans Inflammation / pathology* Kidney Tubules / drug effects Kidney Tubules / pathology Male Membrane Proteins / metabolism* Mice, Inbred C57BL Mitochondria / drug effects Mitochondria / metabolism Mitochondria / pathology* Neutrophils / drug effects Neutrophils / metabolism Nucleotidyltransferases / metabolism* Signal Transduction / drug effects bcl-2-Associated X Protein / metabolism |
| IF | 8.109 |
| Times Cited | 15 |
| Altmetric score |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 72 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Mice | RBRC09881 |