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Kidney Week

Abstract: TH-PO473

Grape Seed Proanthocyanidin Extract Alleviates Renal Fibrosis by Inhibiting the Activation of the C3/HMGB1/TGF-β Pathway

Session Information

  • CKD: Mechanisms - I
    November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Wang, Kun, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
  • Wei, Haotian, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
  • Liu, Yanyan, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
  • Xu, Gang, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
Background

Grape seed proanthocyanidin extract (GSPE) has been reported to exhibit a variety of protective effects, such as antioxidant, anti-tumor, anti-aging, hypoglycemic, anti-atherosclerosis and other pharmacological effects. Kidney disease is usually a pathogenic immune response to the kidney's autoantigen or local autoimmune response. As a member of the complement system, complement component 3 (C3) deposited in the kidney is now recognized as an important causative mediator of various human 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.

Methods

Eight-week-old C57bl/6 mice were subjected to unilateral ureteral occlusion (UUO) with or without GSPE administration. Pathological damage, collagen deposition, interstitial inflammation and renal fibrosis were detected by histological staining, immunofluorescence and Western Blot. For the in vitro studies, mouse primary renal tubular epithelial cells (PTECs) and NRK-49F were used. In order to find possible inhibition targets for GSPE, we used complement C3 (C3a), HMGB1 and TGF-β1 to stimulate PTECs or NRK-49F, then the fibrosis-related proteins and inflammatory factor were analyzed by immunofluorescence, Western Blot or rt-PCR.

Results

In vivo, we observed that administration of GSPE relieves inflammation and chronic renal fibrosis in mouse models of UUO (unilateral ureteral obstruction). Our data indicated that GSPE inhibited C3 secreted by macrophages to relieve renal interstitial inflammation. In vitro, we found that C3 could stimulate HMGB1 translocation form nucleus to cytoplasm and promote the expression of pro-inflammatory cytokines including TGF-β1 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-β1 pathway. In addition, the myofibroblast activation was inhibited by GSPE via TGF-β1 /Smad2/3signaling pathways in normal rat kidney fibroblast (NRK-49F) cells.

Conclusion

Taken together, these observations provide that GSPE alleviates renal fibrosis by inhibiting the activation of C3/ HMGB1/ TGF-β pathway and could thus lead to find the potential therapy for the suppression of renal fibrosis.