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• W3000726246 endingPage "2016" @default.
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• W3000726246 abstract "Sustained macroautophagy/autophagy favors the differentiation of fibroblasts into myofibroblasts. Cellular senescence, another means of responding to long-term cellular stress, has also been linked to myofibroblast differentiation and fibrosis. Here, we evaluate the relationship between senescence and myofibroblast differentiation in the context of sustained autophagy. We analyzed markers of cell cycle arrest/senescence in fibroblasts in vitro, where autophagy was triggered by serum starvation (SS). Autophagic fibroblasts expressed the senescence biomarkers CDKN1A/p21 and CDKN2A/p16 and exhibited increased senescence-associated GLB1/beta-galactosidase activity. Inhibition of autophagy in serum-starved fibroblasts with 3-methyladenine, LY294002, or ATG7 (autophagy related 7) silencing prevented the expression of senescence-associated markers. Similarly, suppressing MTORC2 activation using rapamycin or by silencing RICTOR also prevented senescence hallmarks. Immunofluorescence microscopy showed that senescence and myofibroblast differentiation were induced in different cells, suggesting mutually exclusive activation of senescence and myofibroblast differentiation. Reactive oxygen species (ROS) are known inducers of senescence and exposing fibroblasts to ROS scavengers decreased ROS production during SS, inhibited autophagy, and significantly reduced the expression of senescence and myofibroblast differentiation markers. ROS scavengers also curbed the AKT1 phosphorylation at Ser473, an MTORC2 target, establishing the importance of ROS in fueling MTORC2 activation. Inhibition of senescence by shRNA to TP53/p53 and shRNA CDKN2A/p16 increased myofibroblast differentiation, suggesting a negative feedback loop of senescence on autophagy-induced myofibroblast differentiation. Collectively, our results identify ROS as central inducers of MTORC2 activation during chronic autophagy, which in turn fuels senescence activation and myofibroblast differentiation in distinct cellular subpopulations.Abbreviations: 3-MA: 3-methyladenine; ACTA2: actin, alpha 2, smooth muscle, aorta; AKT1: AKT serine/threonine kinase 1; p-AKT1: AKT1 Ser473 phosphorylation; t-AKT1: total AKT serine/threonine kinase 1; ATG4A: autophagy related 4A cysteine peptidase; ATG7: autophagy gene 7; C12FDG: 5-dodecanoylaminofluorescein Di-β-D-Galactopyranoside; CDKN1A: cyclin dependent kinase inhibitor 1A; CDKN2A: cyclin dependent kinase inhibitor 2A; Ctl: control; DAPI: 4ʹ,6-diamidino-2-phenylindole, dilactate; ECM: extracellular matrix; GSH: L-glutathione reduced; H2O2: hydrogen peroxide; HLF: adult human lung fibroblasts; Ho: Hoechst 33342 (2′‐[4‐ethoxyphenyl]‐5‐[4‐methyl‐1‐piperazinyl]‐2.5′‐bi‐1H‐benzimidazole); HSC: hepatic stellate cells; LY: LY294002; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MTORC1/2: mechanistic target of rapamycin kinase complex 1/2; N: normal growth medium; NAC: N-acetyl-L-cysteine; PBS: phosphate-buffered saline; PDGFA: platelet derived growth factor subunit A; PRKCA/PKCα: protein kinase C alpha; PtdIns3K: class III phosphatidylinositol 3-kinase; PTEN: phosphatase and tensin homolog; R: rapamycin; RICTOR: RPTOR independent companion of MTOR complex 2; ROS: reactive oxygen species; RPTOR: regulatory associated protein of MTOR complex 1; SA-GLB1/β-gal: senescence-associated galactosidase beta 1; SGK1: serum/glucocorticoid regulated kinase 1; shRNA: short hairpin RNA; siCtl: control siRNA; siRNA: small interfering RNA; SQSTM1: sequestosome 1; SS: serum-free (serum starvation) medium; TP53: tumor protein p53; TUBA: tubulin alpha; V: vehicle." @default.
• W3000726246 created "2020-01-23" @default.
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• W3000726246 date "2020-01-13" @default.
• W3000726246 modified "2023-10-11" @default.
• W3000726246 title "Autophagy drives fibroblast senescence through MTORC2 regulation" @default.
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• W3000726246 cites W1642162311 @default.
• W3000726246 cites W1819877893 @default.
• W3000726246 cites W1963790204 @default.
• W3000726246 cites W1965718763 @default.
• W3000726246 cites W1966672647 @default.
• W3000726246 cites W1973256609 @default.
• W3000726246 cites W1977362098 @default.
• W3000726246 cites W1978593002 @default.
• W3000726246 cites W1983698019 @default.
• W3000726246 cites W1986014209 @default.
• W3000726246 cites W1987566410 @default.
• W3000726246 cites W1989500240 @default.
• W3000726246 cites W1996113298 @default.
• W3000726246 cites W2005270729 @default.
• W3000726246 cites W2010345740 @default.
• W3000726246 cites W2010417927 @default.
• W3000726246 cites W2013537969 @default.
• W3000726246 cites W2016193552 @default.
• W3000726246 cites W2021163182 @default.
• W3000726246 cites W2021835404 @default.
• W3000726246 cites W2023359623 @default.
• W3000726246 cites W2030795773 @default.
• W3000726246 cites W2031881900 @default.
• W3000726246 cites W2035537270 @default.
• W3000726246 cites W2037689922 @default.
• W3000726246 cites W2061619522 @default.
• W3000726246 cites W2077450385 @default.
• W3000726246 cites W2078281194 @default.
• W3000726246 cites W2079355772 @default.
• W3000726246 cites W2082525702 @default.
• W3000726246 cites W2082796078 @default.
• W3000726246 cites W2097165440 @default.
• W3000726246 cites W2103078762 @default.
• W3000726246 cites W2113995129 @default.
• W3000726246 cites W2114806766 @default.
• W3000726246 cites W2116054786 @default.
• W3000726246 cites W2124614845 @default.
• W3000726246 cites W2127063807 @default.
• W3000726246 cites W2131089732 @default.
• W3000726246 cites W2132224453 @default.
• W3000726246 cites W2145265436 @default.
• W3000726246 cites W2146226846 @default.
• W3000726246 cites W2146887271 @default.
• W3000726246 cites W2151381771 @default.
• W3000726246 cites W2153747430 @default.
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• W3000726246 doi "https://doi.org/10.1080/15548627.2020.1713640" @default.
• W3000726246 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7595590" @default.
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