Targeting histone methyltransferase enhancer of zeste homolog-2 inhibits renal epithelial-mesenchymal transition and attenuates renal fibrosis

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Xiaoxu ZhouShougang Zhuang

Abstract

Enhancer of zeste homolog-2 (EZH2) is a methyltransferase that induces histone H3 lysine 27 trimethylation (H3K27me3) and functions as an oncogenic factor in many cancer types. Its role in renal epithelial-mesenchymal transition (EMT) remains unknown. In this study, we found that EZH2 and H3K27me3 were highly expressed in mouse kidney with unilateral ureteral obstruction and cultured mouse kidney proximal tubular (TKPT) cells undergoing EMT. Inhibition of EZH2 with 3-deazaneplanocin A (3-DZNeP) attenuated renal fibrosis, which was associated with preserving E-cadherin expression and inhibiting Vimentin up-regulation in the obstructed kidney. Treatment with 3-DZNeP or transfection of EZH2 siRNA also inhibited TGF-β1-induced EMT of TKPT cells. Injury to the kidney or cultured TKPT cells resulted in up-regulation of Snail-l family transcriptional repressor (Snail)-1 and Twist family basic helix-loop-helix (BHLH) transcription factor (Twist)-1, which are 2 transcription factors, and down-regulation of phosphatase and tensin homolog, a protein tyrosine phosphatase associated with inhibition of PI3K-protein kinase B (AKT) signaling; EZH2 inhibition or silencing reversed all those responses. 3-DZNeP was also effective in suppressing e...Continue Reading

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Citations

Dec 24, 2019·Frontiers in Pharmacology·Chao Yu, Shougang Zhuang
Mar 2, 2019·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Hua LiangHong-Zhen Liu
Mar 22, 2019·Nature Reviews. Nephrology·Mitsuo Kato, Rama Natarajan
Dec 15, 2020·Current Opinion in Organ Transplantation·Thomas RousselleValeria R Mas
Mar 9, 2021·Frontiers in Physiology·Tingting LiShougang Zhuang
Dec 28, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xiaoqin ZhangXiaogang Li

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