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

Scientific Reports
Ling WangZhi-Hong Liu

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...Continue Reading

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Citations

Jul 20, 2019·Journal of Applied Toxicology : JAT·Jingting HuoLuyong Zhang
Jun 12, 2019·Oxidative Medicine and Cellular Longevity·Yang FengYunyou Duan
Dec 16, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Mengjie SunZhihong Liu
Dec 16, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yi-Qi YangPeng Xu
Oct 27, 2021·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Jianyao ShenChaoquan Wang

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Methods Mentioned

BETA
transgenic
ELISA
immunoprecipitation
electrophoresis
transfection
PCR

Software Mentioned

KEGG Pathway Analysis
Image Pro Plus
Cellquest
FACScan
SPSS

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis