Hydrostatic Pressure Induces Activation of Astrocytes through the JAK2/STAT3 Pathway
JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS(2024)
摘要
Background: Glaucoma, characterized by retinal ganglion cell axons and optic disc cupping degeneration, is strongly associated with elevated intraocular pressure. This study aimed to elucidate the potential role and underlying mechanisms of hydrostatic pressure in the activation of astrocytes. Methods: Astrocytes were subjected to 0 mmHg in the incubator or to hydrostatic pressure in 20, 30, 40, 50 and 60 mmHg in a pressurized incubator for 24 hours. Additionally, astrocytes were treated with varying concentrations of AG490 (10, 15, or 20 mu M) under 40 mmHg pressure. The expressions of glial fibrillary acidic protein (GFAP), interleukin (IL)-1 beta, tumor necrosis factor-alpha (TNF-alpha), IL-6, inducible nitric oxide synthase (iNOS), and Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway-related proteins were analyzed using Western blot or real-time reverse transcription quantitative polymerase chain reaction. Results: Hydrostatic pressure significantly increased the mRNA and protein expression of GFAP (p < 0.05), elevated the mRNA levels of IL-1 beta, TNF-alpha, IL-6, and iNOS in astrocytes (p < 0.05), and enhanced the levels of IL-1 beta, TNF-alpha, IL-6, and NO in astrocytes supernatants (p < 0.05). Furthermore, the JAK2/STAT3 signaling pathway was activated in response to hydrostatic pressure (p < 0.05). Treatment with AG490 mitigated the effects of hydrostatic pressure on GFAP, IL-1 beta, TNF-alpha, IL-6, iNOS expression, and JAK2/STAT3 pathway activation (p < 0.05). Conclusions: Hydrostatic pressure induces the activation of astrocytes and inflammation through the promotion of the JAK2/STAT3 signaling pathway. Therefore, the JAK2/STAT3 pathway is a promising target to control the activation of astrocyte in glaucoma.
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关键词
glaucoma,hydrostatic pressure,JAK2,STAT3
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