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Resveratrol alleviates inflammatory bowel disease by inhibiting JAK2/STAT3 pathway activity via the reduction of O-GlcNAcylation of STAT3 in intestinal epithelial cells.
Yaqin, Zhang; Kehan, Wu; Yi, Zhu; Naijian, Wang; Wei, Qiu; Fei, Mao.
Afiliación
  • Yaqin Z; Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, PR China.; Department of Laboratory Medicine, Shanghai Geriatric Medical Center, Shanghai 201102, China.
  • Kehan W; Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, PR China.
  • Yi Z; The People's Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Zhenjiang, Jiangsu 212300, China.
  • Naijian W; Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, PR China.
  • Wei Q; Nanjing Jiangning Hospital, Nanjing, Jiangsu 211100, China. Electronic address: qw18068809231@163.com.
  • Fei M; Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, PR China.. Electronic address: maofei2003@ujs.edu.cn.
Toxicol Appl Pharmacol ; 484: 116882, 2024 Mar.
Article en En | MEDLINE | ID: mdl-38437956
ABSTRACT
The role of O-linked N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) in the pathogenesis of inflammatory bowel disease (IBD) has been increasingly highlighted in recent studies. It's been reported that signal transducer and activator of transcription 3 (STAT3) O-GlcNAcylation can affect the activity of the Janus kinase2 (JAK2)/STAT3 pathway.Our recent study showed that resveratrol repairsIBDin mice.On this basis,the present study aimed to explore whether the mechanism of IBD repair by resveratrol is associated with STAT3 O-GlcNAcylation. Pretreatment of colitis mice and intestinal epithelial cells with an O-GlcNAcylation promoter (Thiamet G, or Glucosamine) and an O-GlcNAcylation inhibitor (OSMI-1) showed that increased O-GlcNAcylation promoted colitis in mice.The pro-inflammatory cytokines interleukin (IL) -6, IL-1ß, and tumor necrosis factor-α (TNF-α) were increased, while the anti-inflammatory cytokine IL-10 was decreased. Moreover, the downstream target proteins of JAK2/STAT3, cyclooxygenase-2 and nitric oxide synthase 2 were up-regulated, Resveratrol treatment mitigated the inflammation by decreasing JAK2/STAT3 activity, as well as STAT3 O-GlcNAcylation. Finally, the correlation between STAT3 glycosylation and phosphorylation in intestinal epithelial cells under the effect of resveratrol was investigated by Immunofluorescence co-localization and immunoprecipitation.The results showed that resveratrol inhibited STAT3 O-GlcNAcylation, thereby inhibiting its phosphorylation, reducing JAK2/STAT3 pathway activity, and alleviating IBD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Inflamatorias del Intestino / Colitis Límite: Animals Idioma: En Revista: Toxicol Appl Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Inflamatorias del Intestino / Colitis Límite: Animals Idioma: En Revista: Toxicol Appl Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos