PUBLICATION
Triptolide preserves glomerular barrier function via the inhibition of p53-mediated increase of GADD45B
- Authors
- Zhai, X., Wang, L., Xu, C., Hou, Q., Zhang, L., Li, Z., Qin, W., Liu, Z., Chen, Z.
- ID
- ZDB-PUB-190724-27
- Date
- 2019
- Source
- Archives of biochemistry and biophysics 671: 210-217 (Journal)
- Registered Authors
- Chen, Zhaohong, Hou, Qing, Liu, Zhihong, Li, Zhi, Wang, Ling, Zhang, Liwen
- Keywords
- none
- MeSH Terms
-
- Animals
- Antigens, Differentiation/metabolism*
- Diterpenes/pharmacology*
- Edema/chemically induced
- Epoxy Compounds/pharmacology
- Glomerular Filtration Barrier/drug effects*
- Metronidazole
- NF-kappa B/metabolism
- Phenanthrenes/pharmacology*
- Podocytes/drug effects
- Podocytes/metabolism
- Protein Binding/drug effects
- Puromycin Aminonucleoside
- Signal Transduction/drug effects
- Tumor Suppressor Protein p53/metabolism*
- Yolk Sac/pathology
- Zebrafish
- Zebrafish Proteins/metabolism*
- PubMed
- 31330131 Full text @ Arch. Biochem. Biophys.
Citation
Zhai, X., Wang, L., Xu, C., Hou, Q., Zhang, L., Li, Z., Qin, W., Liu, Z., Chen, Z. (2019) Triptolide preserves glomerular barrier function via the inhibition of p53-mediated increase of GADD45B. Archives of biochemistry and biophysics. 671:210-217.
Abstract
Podocytes are important to glomerular filtration barrier integrity and maintenance of size selectivity in protein filtration in the kidney. Although there is evidence to suggest that triptolide has direct protective effects on podocyte injuries, the mechanism mediating this process remains largely unexplored. In this study, we found triptolide suppresses podocyte p53 and GADD45B expression in vivo and in vitro. We used our previously developed in vivo zebrafish model of inducible podocyte-targeted injury and found that triptolide or the inhibition of p53 and gadd45ba with morpholino (MO) alleviated metronidazole (MTZ) induced edema in zebrafish, while the overexpression of gadd45ba in podocytes blocked the protective effect of triptolide and p53 MO on podocyte injury in zebrafish. Further study showed that p53 directly transactivated GADD45B. Triptolide inhibited p53 binding to the GADD45B promoter and subsequent GADD45B transcription. We further demonstrated that p53 may indirectly regulate GADD45B expression via NF-κB signaling. Taken together, our findings demonstrated that triptolide maintained glomerular barrier function via the inhibition of p53-NF-κB-GADD45B signaling, which provides a new understanding of the antiproteinuric effects of triptolide in glomerular diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping