Mitochondrial Damage Causes Inflammation via cGAS-STING Signaling in Acute Kidney Injury DOI Creative Commons
Hiroshi Maekawa, Tsuyoshi Inoue,

Haruki Ouchi

et al.

Cell Reports, Journal Year: 2019, Volume and Issue: 29(5), P. 1261 - 1273.e6

Published: Oct. 1, 2019

Acute kidney injury (AKI) is characterized by mitochondrial dysfunction and activation of the innate immune system. The cyclic GMP-AMP synthase (cGAS) stimulator interferon genes (STING) pathway detects cytosolic DNA induces immunity. Here, we investigate role damage subsequent cGAS-STING using a genetically engineered animal model cisplatin-induced AKI cultured tubular cells. Cisplatin induced mtDNA leakage into cytosol-probably through BCL-2-like protein 4 (BAX) pores in outer membrane-in tubules, with pathway, thereby triggering inflammation progression, which improved STING-deficient mice. STING knockdown cells ameliorates inflammatory responses cisplatin. depletion repletion studies support via signal mtDNA. Therefore, conclude that mtDNA-cGAS-STING critical regulator injury.

Language: Английский

Cellular senescence in ageing: from mechanisms to therapeutic opportunities DOI
Raffaella Di Micco, Valery Krizhanovsky, Darren J. Baker

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2020, Volume and Issue: 22(2), P. 75 - 95

Published: Dec. 16, 2020

Language: Английский

Citations

1479
The cGAS–STING pathway as a therapeutic target in inflammatory diseases DOI Open Access
Alexiane Decout, Jason D. Katz,

Shankar Venkatraman

et al.

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 21(9), P. 548 - 569

Published: April 8, 2021

Language: Английский

Citations

1369
Molecular mechanisms and cellular functions of cGAS–STING signalling DOI
Karl‐Peter Hopfner, Veit Hornung

Nature Reviews Molecular Cell Biology, Journal Year: 2020, Volume and Issue: 21(9), P. 501 - 521

Published: May 18, 2020

Language: Английский

Citations

1323
DAMP-sensing receptors in sterile inflammation and inflammatory diseases DOI
Tao Gong, Lei Liu, Wei Jiang

et al.

Nature reviews. Immunology, Journal Year: 2019, Volume and Issue: 20(2), P. 95 - 112

Published: Sept. 26, 2019

Language: Английский

Citations

1288
DNA sensing by the cGAS–STING pathway in health and disease DOI
Mona Motwani,

Scott Pesiridis,

Katherine A. Fitzgerald

et al.

Nature Reviews Genetics, Journal Year: 2019, Volume and Issue: 20(11), P. 657 - 674

Published: July 29, 2019

Language: Английский

Citations

1106
Cytoplasmic chromatin triggers inflammation in senescence and cancer DOI
Zhixun Dou,

Kanad Ghosh,

Maria Grazia Vizioli

et al.

Nature, Journal Year: 2017, Volume and Issue: 550(7676), P. 402 - 406

Published: Oct. 1, 2017

Language: Английский

Citations

1072
Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype DOI Creative Commons

Ruchi Kumari,

Parmjit Jat

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: March 29, 2021

Cellular senescence is a stable cell cycle arrest that can be triggered in normal cells response to various intrinsic and extrinsic stimuli, as well developmental signals. Senescence considered highly dynamic, multi-step process, during which the properties of senescent continuously evolve diversify context dependent manner. It associated with multiple cellular molecular changes distinct phenotypic alterations, including proliferation unresponsive mitogenic stimuli. Senescent remain viable, have alterations metabolic activity undergo dramatic gene expression develop complex senescence-associated secretory phenotype. compromise tissue repair regeneration, thereby contributing toward aging. Removal attenuate age-related dysfunction extend health span. also act potent anti-tumor mechanism, by preventing potentially cancerous cells. program acts double-edged sword, both beneficial detrimental effects on organism, an example evolutionary antagonistic pleiotropy. Activation p53/p21 WAF1/CIP1 p16 INK4A /pRB tumor suppressor pathways play central role regulating senescence. Several other recently been implicated mediating Herein we review mechanisms underlie growth particular focus why stop dividing, stability arrest, hypersecretory phenotype how different are all integrated.

Language: Английский

Citations

1043
Senescence and aging: Causes, consequences, and therapeutic avenues DOI Creative Commons
Domhnall McHugh, Jesús Gil

The Journal of Cell Biology, Journal Year: 2017, Volume and Issue: 217(1), P. 65 - 77

Published: Nov. 7, 2017

Aging is the major risk factor for cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. Although we are far from understanding biological basis of aging, research suggests that targeting aging process itself could ameliorate many age-related pathologies. Senescence a cellular response characterized by stable growth arrest other phenotypic alterations include proinflammatory secretome. plays roles in normal development, maintains tissue homeostasis, limits tumor progression. However, senescence has also been implicated as cause disease. In this regard, recent experimental evidence shown genetic or pharmacological ablation senescent cells extends life span improves health span. Here, review molecular links between discuss novel therapeutic avenues connection opens.

Language: Английский

Citations

1029
The cGAS–cGAMP–STING pathway connects DNA damage to inflammation, senescence, and cancer DOI Creative Commons
Tuo Li, Zhijian J. Chen

The Journal of Experimental Medicine, Journal Year: 2018, Volume and Issue: 215(5), P. 1287 - 1299

Published: April 5, 2018

Detection of microbial DNA is an evolutionarily conserved mechanism that alerts the host immune system to mount a defense response infections. However, this detection also poses challenge as how distinguish foreign from abundant self-DNA. Cyclic guanosine monophosphate (GMP)-adenosine (AMP) synthase (cGAS) sensor triggers innate responses through production second messenger cyclic GMP-AMP (cGAMP), which binds and activates adaptor protein STING. cGAS can be activated by double-stranded irrespective sequence, including Although normally kept inactive in cells still not well understood, recent research has provided strong evidence genomic damage leads activation stimulate inflammatory responses. This review summarizes findings on instability trigger serves link inflammation, cellular senescence, cancer.

Language: Английский

Citations

983
Cellular Senescence: Aging, Cancer, and Injury DOI Open Access
Arianna Calcinotto, Jaskaren Kohli, Elena Zagato

et al.

Physiological Reviews, Journal Year: 2019, Volume and Issue: 99(2), P. 1047 - 1078

Published: Jan. 16, 2019

Cellular senescence is a permanent state of cell cycle arrest that occurs in proliferating cells subjected to different stresses. Senescence is, therefore, cellular defense mechanism prevents the acquire an unnecessary damage. The senescent accompanied by failure re-enter response mitogenic stimuli, enhanced secretory phenotype and resistance death. takes place several tissues during physiological pathological processes such as tissue remodeling, injury, cancer, aging. Although one causative aging it responsible aging-related disorders, can also play positive role. In embryogenesis are required for proper development embryo repair. works potent barrier prevent tumorigenesis. Therefore, identification characterization key features senescence, induction cancer cells, or elimination pharmacological interventions gaining consideration fields research. Here, we describe known cell-autonomous, noncell-autonomous regulators attempt discuss functional role this fundamental process contexts light novel therapeutic targets.

Language: Английский

Citations

961