Wogonin upregulates SOCS3 to alleviate the injury in Diabetic Nephropathy by inhibiting TLR4-mediated JAK/STAT/AIM2 signaling pathway.
Mol Med
; 30(1): 78, 2024 Jun 06.
Article
em En
| MEDLINE
| ID: mdl-38844873
ABSTRACT
BACKGROUND:
Diabetic nephropathy (DN) is a life-threatening renal disease and needs urgent therapies. Wogonin is renoprotective in DN. This study aimed to explore the mechanism of how wogonin regulated high glucose (HG)-induced renal cell injury.METHODS:
Diabetic mice (db/db), control db/m mice, and normal glucose (NG)- or HG-treated human tubule epithelial cells (HK-2) were used to evaluate the levels of suppressor of cytokine signaling 3 (SOCS3), Toll-like receptor 4 (TLR4), inflammation and fibrosis. Lentivirus was used to regulate SOCS3 and TLR4 expressions. After oral gavage of wogonin (10 mg/kg) or vehicle in db/db mice, histological morphologies, blood glucose, urinary protein, serum creatinine values (Scr), blood urea nitrogen (BUN), superoxide dismutase (SOD), glutathione (GSH), and reactive oxygen species (ROS) were assessed. RT-qPCR and Western blot evaluated inflammation and fibrosis-related molecules.RESULTS:
HG exposure induced high blood glucose, severe renal injuries, high serumal Src and BUN, low SOD and GSH, and increased ROS. HG downregulated SOCS3 but upregulated TLR4 and JAK/STAT, fibrosis, and inflammasome-related proteins. Wogonin alleviated HG-induced renal injuries by decreasing cytokines, ROS, Src, and MDA and increasing SOD and GSH. Meanwhile, wogonin upregulated SOCS3 and downregulated TLR4 under HG conditions. Wogonin-induced SOCS3 overexpression directly decreased TLR4 levels and attenuated JAK/STAT signaling pathway-related inflammation and fibrosis, but SOCS3 knockdown significantly antagonized the protective effects of wogonin. However, TLR4 knockdown diminished SOCS3 knockdown-induced renal injuries.CONCLUSION:
Wogonin attenuates renal inflammation and fibrosis by upregulating SOCS3 to inhibit TLR4 and JAK/STAT pathway.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Flavanonas
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Nefropatias Diabéticas
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Receptor 4 Toll-Like
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Proteína 3 Supressora da Sinalização de Citocinas
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
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REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM