PUBLICATION

Triptolide attenuates proteinuria and podocyte apoptosis via inhibition of NF-κB/GADD45B

Authors
Wang, L., Zhang, L., Hou, Q., Zhu, X., Chen, Z., Liu, Z.
ID
ZDB-PUB-180720-6
Date
2018
Source
Scientific Reports   8: 10843 (Journal)
Registered Authors
Chen, Zhaohong, Hou, Qing, Liu, Zhihong, Wang, Ling, Zhang, Liwen
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Anti-Infective Agents/toxicity
  • Antigens, Differentiation/chemistry*
  • Antigens, Differentiation/genetics
  • Antigens, Differentiation/metabolism
  • Apoptosis/drug effects*
  • Cells, Cultured
  • Diterpenes/pharmacology*
  • Epoxy Compounds/pharmacology
  • Humans
  • Immunosuppressive Agents/pharmacology
  • Metronidazole/toxicity
  • NF-kappa B/antagonists & inhibitors*
  • NF-kappa B/genetics
  • NF-kappa B/metabolism
  • Phenanthrenes/pharmacology*
  • Podocytes/cytology
  • Podocytes/drug effects*
  • Podocytes/metabolism
  • Proteinuria/chemically induced
  • Proteinuria/drug therapy*
  • Proteinuria/metabolism
  • Proteinuria/pathology
  • Zebrafish
  • Zebrafish Proteins/antagonists & inhibitors*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
30022148 Full text @ Sci. Rep.
Abstract
Podocyte injury is a primary contributor to proteinuria. Triptolide is a major active component of Tripterygium wilfordii Hook F that exhibits potent antiproteinuric effects. We used our previously developed in vivo zebrafish model of inducible podocyte-target injury and found that triptolide treatment effectively alleviated oedema, proteinuria and foot process effacement. Triptolide also inhibited podocyte apoptosis in our zebrafish model and in vitro. We also examined the mechanism of triptolide protection of podocyte. Whole-genome expression profiles of cultured podocytes demonstrated that triptolide treatment downregulated apoptosis pathway-related GADD45B expression. Specific overexpression of gadd45b in zebrafish podocytes abolished the protective effects of triptolide. GADD45B is a mediator of podocyte apoptosis that contains typical NF-κB binding sites in the promoter region, and NF-κB p65 primarily transactivates this gene. Triptolide inhibited NF-κB signalling activation and binding of NF-κB to the GADD45B promoter. Taken together, our findings demonstrated that triptolide attenuated proteinuria and podocyte apoptosis via inhibition of NF-κB/GADD45B signalling, which provides a new understanding of the antiproteinuric effects of triptolide in glomerular diseases.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes