PMID- 32642006
OWN - NLM
STAT- MEDLINE
DCOM- 20210503
LR  - 20210503
IS  - 1838-7640 (Electronic)
IS  - 1838-7640 (Linking)
VI  - 10
IP  - 16
DP  - 2020
TI  - Sirt6 deficiency aggravates angiotensin II-induced cholesterol accumulation and 
      injury in podocytes.
PG  - 7465-7479
LID - 10.7150/thno.45003 [doi]
AB  - Disturbed renal lipid metabolism, especially cholesterol dysregulation plays a 
      crucial role in the pathogenesis of chronic kidney disease (CKD). We recently 
      reported that angiotensin (Ang) II could induce cholesterol accumulation and 
      injury in podocytes. However, the underlying mechanisms for these alterations 
      remain unknown. Methods: Bioinformatics analysis of renal biopsy specimens from 
      patients with hypertensive nephropathy (HN) suggests the involvement of Sirtuin 6 
      (Sirt6) in Ang II-induced dysregulation of glomerular cholesterol. Using a 
      podocyte-specific Sirt6 knockout mouse model, the effects of Sirt6 on Ang 
      II-induced cholesterol accumulation in podocytes and the therapeutic efficacies 
      of cholesterol-lowering agents were evaluated. Results: Cholesterol accumulation 
      was detected in the podocytes of Ang II-infused mice, whereas selective deletion 
      of Sirt6 in podocytes not only increased cholesterol accumulation in these cells 
      but also exacerbated Ang II-induced kidney injury. Deletion of Sirt6 also 
      attenuated the protective effect of cyclodextrin (CD) on Ang II-induced urinary 
      albumin excretion, glomerulosclerosis and podocyte injury. In addition, we 
      demonstrated that Sirt6 affected cholesterol efflux in podocytes by regulating 
      the expression of ATP-binding cassette transporter G1 (ABCG1). Conclusions: These 
      findings provide evidence that Sirt6 is a potential target for renin-angiotensin 
      system (RAS)-associated podocyte injury and provide a rationale for the 
      application of cholesterol-lowering agents in patients with CKD.
CI  - (c) The author(s).
FAU - Yang, Qian
AU  - Yang Q
AD  - Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
AD  - Nephrology and Urology Research Institute of Wuhan University, Wuhan, Hubei, 
      China.
FAU - Hu, Jijia
AU  - Hu J
AD  - Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
AD  - Nephrology and Urology Research Institute of Wuhan University, Wuhan, Hubei, 
      China.
FAU - Yang, Yingjie
AU  - Yang Y
AD  - Nephrology and Urology Research Institute of Wuhan University, Wuhan, Hubei, 
      China.
FAU - Chen, Zhaowei
AU  - Chen Z
AD  - Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
AD  - Nephrology and Urology Research Institute of Wuhan University, Wuhan, Hubei, 
      China.
FAU - Feng, Jun
AU  - Feng J
AD  - Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
AD  - Nephrology and Urology Research Institute of Wuhan University, Wuhan, Hubei, 
      China.
FAU - Zhu, Zijing
AU  - Zhu Z
AD  - Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
AD  - Nephrology and Urology Research Institute of Wuhan University, Wuhan, Hubei, 
      China.
FAU - Wang, Huiming
AU  - Wang H
AD  - Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
AD  - Nephrology and Urology Research Institute of Wuhan University, Wuhan, Hubei, 
      China.
FAU - Yang, Dingping
AU  - Yang D
AD  - Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
AD  - Nephrology and Urology Research Institute of Wuhan University, Wuhan, Hubei, 
      China.
FAU - Liang, Wei
AU  - Liang W
AD  - Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
AD  - Nephrology and Urology Research Institute of Wuhan University, Wuhan, Hubei, 
      China.
FAU - Ding, Guohua
AU  - Ding G
AD  - Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
AD  - Nephrology and Urology Research Institute of Wuhan University, Wuhan, Hubei, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200612
PL  - Australia
TA  - Theranostics
JT  - Theranostics
JID - 101552395
RN  - 0 (Anticholesteremic Agents)
RN  - 11128-99-7 (Angiotensin II)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 2.4.2.31 (Sirt6 protein, mouse)
RN  - EC 3.5.1.- (SIRT6 protein, human)
RN  - EC 3.5.1.- (Sirtuins)
SB  - IM
MH  - Adult
MH  - Angiotensin II/administration & dosage/toxicity
MH  - Animals
MH  - Anticholesteremic Agents/pharmacology/therapeutic use
MH  - Biopsy
MH  - Case-Control Studies
MH  - Cell Line
MH  - Cholesterol/blood/*metabolism
MH  - Datasets as Topic
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Expression Profiling
MH  - Humans
MH  - Lipid Metabolism/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Middle Aged
MH  - Oligonucleotide Array Sequence Analysis
MH  - Podocytes/drug effects/*pathology
MH  - Renal Insufficiency, Chronic/blood/chemically induced/drug therapy/*pathology
MH  - Sirtuins/*deficiency/genetics/*metabolism
PMC - PMC7330847
OTO - NOTNLM
OT  - Sirt6
OT  - angiotensin II
OT  - cholesterol accumulation
OT  - methyl-beta-cyclodextrin
OT  - podocyte injury
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2020/07/10 06:00
MHDA- 2021/05/04 06:00
PMCR- 2020/01/01
CRDT- 2020/07/10 06:00
PHST- 2020/02/17 00:00 [received]
PHST- 2020/05/28 00:00 [accepted]
PHST- 2020/07/10 06:00 [entrez]
PHST- 2020/07/10 06:00 [pubmed]
PHST- 2021/05/04 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - thnov10p7465 [pii]
AID - 10.7150/thno.45003 [doi]
PST - epublish
SO  - Theranostics. 2020 Jun 12;10(16):7465-7479. doi: 10.7150/thno.45003. eCollection 
      2020.