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Neurochem Res ; 46(9): 2387-2402, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34145502

RESUMO

To investigate the influence of tumor necrosis factor-stimulated gene-6 (TSG-6) secreted by bone mesenchymal stem cells (BMSCs) on blood brain barrier (BBB) after intracerebral hemorrhage (ICH) and its related mechanisms. BMSCs and astrocytes were isolated and induced by TNF-α and LPS respectively. The effect of TSG-6 secreted by BMSCs on the proliferation and apoptosis of astrocytes and inflammatory response were assessed by CCK8, flow cytometry, and ELISA respectively. Then we studied the effects of TSG-6 secreted by BMSCs through the paracrine mechanism on the integrity of BBB after ICH via NF-κB signaling pathway in vitro and in vivo. We successfully isolated BMSCs and astrocytes. After LPS treatment of astrocytes, IL-1ß, IL-6, and TNF-α showed an upward trend. TSG-6 secreted by TNF-α-activated BMSCs could antagonize the inflammatory response in activated astrocytes. Through the co-culture of astrocytes and BMSCs and the ICH animal model, we found that TSG-6 regulates activated astrocytes by inhibiting the NF-κB signaling pathway and ameliorates BBB damage. Furthermore, we found that TNF-α-activated BMSCs secreted exosomes containing TSG-6 and played an anti-inflammatory effect. TSG-6 secreted by BMSCs regulates activated astrocytes by inhibiting the NF-κB signaling pathway, thereby ameliorating BBB damage.


Assuntos
Astrócitos/metabolismo , Barreira Hematoencefálica/fisiologia , Moléculas de Adesão Celular/metabolismo , Hemorragia Cerebral/metabolismo , Células-Tronco Mesenquimais/metabolismo , Transdução de Sinais/fisiologia , Animais , Apoptose/fisiologia , Astrócitos/efeitos dos fármacos , Proliferação de Células/fisiologia , Citocinas/metabolismo , Exossomos/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , NF-kappa B/metabolismo , Ratos Sprague-Dawley
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