Sirtuin 6 is a key contributor to gender differences in acute kidney injury

急性肾损伤 钥匙(锁) 锡尔图因 医学 西妥因1 重症监护医学 老年学 内科学 生物 计算机安全 计算机科学 生物化学 基因 乙酰化 下调和上调
作者
Jinhua Miao,Jiewu Huang,Ye Liang,Yunfang Zhang,Jiemei Li,Ping Meng,Weiwei Shen,Xiaolong Li,Qinyu Wu,Li Wang,Hongxin Niu,Ying Tang,Shan Zhou,Lili Zhou
出处
期刊:Cell death discovery [Springer Nature]
卷期号:9 (1) 被引量:2
标识
DOI:10.1038/s41420-023-01432-y
摘要

Acute kidney injury (AKI) is rapidly increasing nowadays and at a high risk to progress into chronic kidney disease (CKD). Of note, men are more susceptive to AKI, suggesting gender differences in AKI patients. However, the underlying mechanisms remain largely unclear. To test it, we adopted two experimental models of AKI, including ischemia/reperfusion injury and rhabdomyolysis, which were constructed in age-matched male and female mice. We found severe damages of tubular apoptosis, mitochondrial dysfunction, and loss of renal function showing in male mice, while female mice only had very mild injury. We further tested the expression of Sirtuins, and found that female mice could preserve more Sirtuin members' expression in case of kidney damage. Among Sirtuin family, Sirtuin 6 was maximally preserved in injured kidney in female mice, suggesting its important role involved in the gender differences of AKI pathogenesis. We then found that knockdown of androgen receptor (AR) attenuated tubular damage, mitochondrial dysfunction and retarded the loss of renal function. Overexpression of Sirtuin 6 also showed similar results. Furthermore, in cultured tubular cells, dihydrotestosterone (DHT) decreased Sirtuin 6 expression and exacerbated cell apoptosis. Ectopic expression of Sirtuin 6 sufficiently inhibited DHT-induced cell apoptosis. Mechanically, we found AR inhibited Sirtuin 6, leading to the repression of binding of Sirtuin 6 with PGC-1α. This resulted in acetylation of PGC-1α and inhibition of its activity, further triggered the loss of mitochondrial homeostasis. Our results provided new insights to the underlying mechanisms of gender differences in AKI, suggesting Sirtuin 6 maybe a new therapeutic target for preventing AKI in male patients.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
是锦锦呀发布了新的文献求助10
3秒前
5秒前
欢呼白晴完成签到 ,获得积分10
6秒前
8秒前
8秒前
深林狼完成签到,获得积分20
8秒前
10秒前
WANG发布了新的文献求助50
12秒前
jiayou彭完成签到 ,获得积分10
13秒前
毛豆应助沐风采纳,获得10
14秒前
二糖发布了新的文献求助10
15秒前
甜甜蝶发布了新的文献求助10
17秒前
18秒前
langwang完成签到,获得积分10
19秒前
王七七完成签到,获得积分10
20秒前
20秒前
二糖完成签到,获得积分10
22秒前
救驾来迟完成签到,获得积分10
23秒前
26秒前
ccm应助WANG采纳,获得10
26秒前
27秒前
27秒前
西乡塘塘主完成签到,获得积分10
29秒前
大意的念芹完成签到,获得积分10
30秒前
LYY完成签到,获得积分20
30秒前
32秒前
33秒前
王开心发布了新的文献求助10
34秒前
35秒前
搜集达人应助rhopak采纳,获得10
35秒前
36秒前
李好运完成签到 ,获得积分10
37秒前
snow_dragon发布了新的文献求助10
37秒前
38秒前
40秒前
nipanpan发布了新的文献求助10
40秒前
小武哥完成签到 ,获得积分10
42秒前
42秒前
FashionBoy应助polaris采纳,获得10
43秒前
乐乐应助梓齊采纳,获得10
44秒前
高分求助中
The ACS Guide to Scholarly Communication 2500
Artificial Intelligence, Co-Creation and Creativity 1000
Pharmacogenomics: Applications to Patient Care, Third Edition 1000
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
Genera Insectorum: Mantodea, Fam. Mantidæ, Subfam. Hymenopodinæ (Classic Reprint) 800
Ethnicities: Media, Health, and Coping 700
The Neotropical “Polymorphic Earless Praying Mantises”–Part II: Taxonomic Review of the Genera and Checklist of Species (Insecta: Mantodea, Acanthopoidea) 600
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3089812
求助须知:如何正确求助?哪些是违规求助? 2741939
关于积分的说明 7567753
捐赠科研通 2392527
什么是DOI,文献DOI怎么找? 1268808
科研通“疑难数据库(出版商)”最低求助积分说明 614174
版权声明 598710