RRC ID 59992
Author Zhai X, Wang L, Xu C, Hou Q, Zhang L, Li Z, Qin W, Liu Z, Chen Z.
Title Triptolide preserves glomerular barrier function via the inhibition of p53-mediated increase of GADD45B.
Journal Arch Biochem Biophys
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.
Volume 671
Pages 210-217
Published 2019-8-15
DOI 10.1016/j.abb.2019.07.012
PII S0003-9861(19)30309-1
PMID 31330131
MeSH 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*
IF 3.559
Times Cited 0
Zebrafish Tg(UAS:nfsB-mCherry)