EZH2 plays a crucial role in ischemia/reperfusion-induced acute kidney injury by regulating p38 signaling

Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]
Hua LiangHong Zhen Liu

Abstract

Renal ischemia-reperfusion (IR)-induced acute kidney injury (AKI) remains a major challenge in clinic. The histone methyltransferases enhancer of zest homolog-2 (EZH2) is associated with the development of renal injury. However, the molecular mechanism has not been fully elucidated. AKI in C57BL/6 mice was generated by renal IR. The 3-deazaneplanocin A (DZNeP), a selective EZH2 inhibitor, or vehicle was administrated in mice after IR. HK-2 cells were exposed to hypoxia-reoxygenation (H/R) stress. Apoptosis was detected by TUNEL assay or flow cytometry. EZH2, caspase-3, p38, F4/80+ macrophages, and CD3+ T cells were examined by immunohistochemistry or Western blot. Tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, IL-6, and IL-18 were measured using RT-PCR. Mice treated with DZNeP exhibited less severe renal dysfunction and tubular injury following IR. EZH2 inhibition decreased apoptotic cells while reducing activation of caspase-3 in kidneys under IR condition. Moreover, EZH2 inhibition impaired the recruitment of CD3+ T cells and F4/80+ cells in kidneys with IR. Administration of DZNeP suppressed the production of TNF-α, MCP-1, IL-6, and IL-18 in IR-treated kidneys. Of note, EZH2 inhibition reduced p38 p...Continue Reading

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Citations

Sep 11, 2019·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Lara Valiño-RivasMaria Dolores Sanchez-Niño
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hao LiuLei Wang
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Mar 9, 2021·Frontiers in Physiology·Tingting LiShougang Zhuang

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Methods Mentioned

BETA
PCR
flow cytometry

Software Mentioned

ImageJ

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