Overexpressed SIRT6 attenuates cisplatin-induced acute kidney injury by inhibiting ERK1/2 signaling.

Abstract:

:Sirtuin 6 (SIRT6) is a NAD+-dependent deacetylase associated with numerous aspects of health and physiology. Overexpression of SIRT6 has emerged as a protector in cardiac tissues against pathologic cardiac hypertrophy. However, the mechanism of this protective effect is not fully understood. Here, both in vivo and in vitro results demonstrated that SIRT6 overexpression can attenuate cisplatin-induced kidney injury in terms of renal dysfunction, inflammation and apoptosis. In addition, SIRT6 knockout aggravated kidney injury caused by cisplatin. We also found that SIRT6 bound to the promoters of ERK1 and ERK2 and deacetylated histone 3 at Lys9 (H3K9) thereby inhibiting ERK1/2 expression. Furthermore, inhibition of ERK1/2 activity eliminated aggravation of kidney injury caused by SIRT6 knock out. Thus, our findings uncover the protective effect of SIRT6 on the kidney and define a new mechanism by which SIRT6 regulates inflammation and apoptosis. This may provide a new therapeutic target for kidney injury under stress.

journal_name

Kidney Int

journal_title

Kidney international

authors

Li Z,Xu K,Zhang N,Amador G,Wang Y,Zhao S,Li L,Qiu Y,Wang Z

doi

10.1016/j.kint.2017.10.021

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

881-892

issue

4

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(17)30801-3

journal_volume

93

pub_type

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