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Clinics (Sao Paulo) ; 79: 100354, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38640751

RESUMO

AIM: The study was to clarify the mechanism of miR-1258 targeting Prep1 (pKnox1) to control Transforming Growth Factor ß1 (TGF-ß1)/SMAD3 pathway in septic Acute Lung Injury (ALI)-induced oxidative stress and inflammation. METHODS: BEAS-2B cells and C57BL/6 mice were used to make in vitro and in vivo septic ALI models, respectively. miR-1258 expression was checked by RT-qPCR. After transfection in the in vitro experimental model, inflammation, oxidative stress, viability, and apoptosis were observed through ELISA, MTT, and flow cytometry. RESULTS: In the in vivo model after miR-1258 overexpression treatment, inflammation, oxidative stress, and lung injury were further investigated. The targeting relationship between miR-1258 and Pknox1 was tested. Low miR-1258 was expressed in septic ALI patients, LPS-treated BEAS-2B cells, and mice. Upregulated miR-1258 prevented inflammation, oxidative stress, and apoptosis but enhanced the viability of LPS-treated BEAS-2B cells. The impact of upregulated miR-1258 on LPS-treated BEAS-2B cells was mitigated by inhibiting Pknox1 expression. MiR-1258 overexpression had the alleviating effects on inflammation, oxidative stress, and lung injury of LPS-injured mice through suppressing Pknox1 expression and TGF-ß1/SMAD3 cascade activation. CONCLUSIONS: The study concludes that miR-1258 suppresses oxidative stress and inflammation in septic ALI through the Pknox1-regulated TGF-ß1/SMAD3 cascade.


Assuntos
Lesão Pulmonar Aguda , Apoptose , Camundongos Endogâmicos C57BL , MicroRNAs , Estresse Oxidativo , Sepse , Proteína Smad3 , Fator de Crescimento Transformador beta1 , Animais , Humanos , Masculino , Camundongos , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismo , Modelos Animais de Doenças , Inflamação/metabolismo , MicroRNAs/metabolismo , MicroRNAs/genética , Sepse/complicações , Sepse/metabolismo , Sepse/genética , Transdução de Sinais , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima
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