GADD45B mediates podocyte injury in zebrafish by activating the ROS-GADD45B-p38 pathway

Cell Death & Disease
Z ChenZ Liu

Abstract

GADD45 gene has been implicated in cell cycle arrest, cell survival or apoptosis in a cell type specific and context-dependent manner. Members of GADD45 gene family have been found differentially expressed in several podocyte injury models, but their roles in podocytes are unclear. Using an in vivo zebrafish model of inducible podocyte injury that we have previously established, we found that zebrafish orthologs of gadd45b were induced upon the induction of podocyte injury. Podocyte-specific overexpression of zebrafish gadd45b exacerbated edema, proteinuria and foot-process effacement, whereas knockdown of gadd45b by morpholino-oligos in zebrafish larvae ameliorated podocyte injury. We then explored the role of GADD45B induction in podocyte injury using in vitro podocyte culture. We confirmed that GADD45B was significantly upregulated during the early phase of podocyte injury in cultured human podocytes and that podocyte apoptosis induced by TGF-β and puromycin aminonucleoside (PAN) was aggravated by GADD45B overexpression but ameliorated by shRNA-mediated GADD45B knockdown. We also showed that ROS inhibitor NAC suppressed PAN-induced GADD45B expression and subsequent activation of p38 MAPK pathway in podocytes and that inhibit...Continue Reading

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Citations

Nov 25, 2016·Cell Death & Disease·Wen-Ting LiuHai-Bo Long
Sep 8, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Henning HagmannPaul T Brinkkoetter
May 22, 2019·Genes·Carlos Camilleri-RoblesMontserrat Corominas
Mar 28, 2021·Journal of the American Society of Nephrology : JASN·Jingping YangZhihong Liu

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Methods Mentioned

BETA
biopsy
transgenic
fluorescence microscopy
ELISA
genotyping
PCR
transfection

Software Mentioned

SPSS
Cellquest
GENE TOOLS
FACScan

Related Concepts

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