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GSPE alleviates renal fibrosis by inhibiting the activation of C3/ HMGB1/ TGF-ß1 pathway.
Wang, Kun; Wei, Haotian; Zhan, Juan; Liang, Xinjun; Zhang, Chunxiu; Liu, Yanyan; Xu, Gang.
Afiliación
  • Wang K; Department of Nephrology, Division of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • Wei H; Department of Nephrology, Division of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • Zhan J; Department of Nephrology, Division of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • Liang X; Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Zhang C; Department of Nephrology, Division of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • Liu Y; Department of Nephrology, Division of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address: liuyy1919@tjh.tjmu.edu.cn.
  • Xu G; Department of Nephrology, Division of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address: xugang@tjh.tjmu.edu.cn.
Chem Biol Interact ; 316: 108926, 2020 Jan 25.
Article en En | MEDLINE | ID: mdl-31874164
Grape seed proanthocyanidin extract (GSPE) has been reported to exhibit a variety of protective effects, such as antioxidant, anti-atherosclerosis and other pharmacological effects. As a member of the complement system, complement component 3 (C3) deposition in the glomerulus is recognized as an important causative mediator of various kidney diseases. In this study, we aimed to identify the effect of GSPE on C3 in the chronic kidney fibrosis and evaluate the possible mechanism. We observed that administration of GSPE relieves inflammation and chronic renal fibrosis in mouse models of UUO. GSPE inhibited C3 secreted by macrophages to relieve renal interstitial inflammation. In vitro, we found that C3 stimulated HMGB1 translocation form nucleus to cytoplasm and promote the expression of pro-inflammatory cytokines including TGF-ß1 in primary renal tubular epithelial cells (PTEC), which could be inhibited by GSPE. Meanwhile, GSPE could also decreased HMGB1-induced EMT of PTEC through suppresses the HMGB1/TLR4/p65/TGF-ß1 pathway. In addition, the myofibroblast activation was inhibited by GSPE via TGF-ß1/Smad2/3 signaling pathways in normal rat kidney fibroblast (NRK-49F) cells. Overall, these observations provide that GSPE alleviates renal fibrosis by inhibiting the C3/HMGB1/TGF-ß1 pathway and could thus lead to find the potential therapy for the suppression of renal fibrosis.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Transducción de Señal / Proantocianidinas / Extracto de Semillas de Uva / Riñón Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Chem Biol Interact Año: 2020 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Transducción de Señal / Proantocianidinas / Extracto de Semillas de Uva / Riñón Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Chem Biol Interact Año: 2020 Tipo del documento: Article País de afiliación: China