PMID- 32702447
OWN - NLM
STAT- MEDLINE
DCOM- 20200917
LR  - 20200917
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 257
DP  - 2020 Sep 15
TI  - Quercetin alleviates kidney fibrosis by reducing renal tubular epithelial cell 
      senescence through the SIRT1/PINK1/mitophagy axis.
PG  - 118116
LID - S0024-3205(20)30867-5 [pii]
LID - 10.1016/j.lfs.2020.118116 [doi]
AB  - Emerging evidence implicates accelerated renal tubular epithelial cell (RTEC) 
      senescence in renal fibrosis progression. Mitophagy protects against kidney 
      injury. However, the mechanistic interplay between cell senescence and mitophagy 
      in RTECs is not clearly defined. The purpose of this study was to evaluate the 
      inhibition of RTEC senescence and renal fibrosis by quercetin and explore the 
      underlying mechanisms. We found that quercetin attenuated RTEC senescence induced 
      by angiotensin II (AngII) in vitro and unilateral ureteral obstruction in vivo. 
      Moreover, we demonstrated that mitochondrial abnormalities such as elevated 
      reactive oxygen species, decreased membrane potential, and fragmentation and 
      accumulation of mitochondrial mass, occurred in AngII-treated RTECs. Quercetin 
      treatment reversed these effects. Furthermore, quercetin enhanced mitophagy in 
      AngII-treated RTECs, which was markedly reduced by treatment with 
      mitophagy-specific inhibitors. Sirtuin-1 (SIRT1) was involved in 
      quercetin-mediated PTEN-induced kinase 1 (PINK1)/Parkin-associated mitophagy 
      activation. Pharmacological antagonism of SIRT1 in AngII-treated RTECs blocked 
      the effects of quercetin on mitophagy and cellular senescence. Finally, quercetin 
      alleviated kidney fibrosis by reducing RTEC senescence via mitophagy. 
      Collectively, the antifibrotic effect of quercetin involved inhibition of RTEC 
      senescence, possibly through activation of SIRT1/PINK1/Parkin-mediated mitophagy. 
      These findings suggest that pharmacological elimination of senescent cells and 
      stimulation of mitophagy represent effective therapeutic strategies to prevent 
      kidney fibrosis.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Liu, Tao
AU  - Liu T
AD  - Department of Pharmacology, College of Pharmacy and Laboratory Medicine, Army 
      Medical University (Third Military Medical University), Chongqing 400038, China.
FAU - Yang, Qunfang
AU  - Yang Q
AD  - Department of Pharmacology, College of Pharmacy and Laboratory Medicine, Army 
      Medical University (Third Military Medical University), Chongqing 400038, China.
FAU - Zhang, Xuan
AU  - Zhang X
AD  - Department of Pharmacology, College of Pharmacy and Laboratory Medicine, Army 
      Medical University (Third Military Medical University), Chongqing 400038, China.
FAU - Qin, Rongxing
AU  - Qin R
AD  - Department of Pharmacology, College of Pharmacy and Laboratory Medicine, Army 
      Medical University (Third Military Medical University), Chongqing 400038, China.
FAU - Shan, Wenjun
AU  - Shan W
AD  - Department of Pharmacology, College of Pharmacy and Laboratory Medicine, Army 
      Medical University (Third Military Medical University), Chongqing 400038, China.
FAU - Zhang, Haigang
AU  - Zhang H
AD  - Department of Pharmacology, College of Pharmacy and Laboratory Medicine, Army 
      Medical University (Third Military Medical University), Chongqing 400038, China.
FAU - Chen, Xiaohong
AU  - Chen X
AD  - Department of Pharmacology, College of Pharmacy and Laboratory Medicine, Army 
      Medical University (Third Military Medical University), Chongqing 400038, China. 
      Electronic address: pharma821@163.com.
LA  - eng
PT  - Journal Article
DEP - 20200720
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Antioxidants)
RN  - 9IKM0I5T1E (Quercetin)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (PTEN-induced putative kinase)
RN  - EC 3.5.1.- (Sirt1 protein, rat)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - Animals
MH  - Antioxidants/*pharmacology/therapeutic use
MH  - Cell Line
MH  - Cellular Senescence/*drug effects
MH  - Epithelium/drug effects
MH  - Fibrosis
MH  - Flow Cytometry
MH  - Kidney/drug effects/*pathology
MH  - Kidney Tubules, Proximal/*drug effects/pathology
MH  - Mitophagy/*drug effects
MH  - Protein Kinases/*metabolism
MH  - Quercetin/*pharmacology/therapeutic use
MH  - Rats
MH  - Sirtuin 1/*metabolism
OTO - NOTNLM
OT  - Fibrosis
OT  - Mitochondria
OT  - Mitophagy
OT  - Quercetin
OT  - Senescence
COIS- Declaration of competing interest The authors declare no conflict of interest.
EDAT- 2020/07/24 06:00
MHDA- 2020/09/18 06:00
CRDT- 2020/07/24 06:00
PHST- 2020/06/05 00:00 [received]
PHST- 2020/07/06 00:00 [revised]
PHST- 2020/07/14 00:00 [accepted]
PHST- 2020/07/24 06:00 [pubmed]
PHST- 2020/09/18 06:00 [medline]
PHST- 2020/07/24 06:00 [entrez]
AID - S0024-3205(20)30867-5 [pii]
AID - 10.1016/j.lfs.2020.118116 [doi]
PST - ppublish
SO  - Life Sci. 2020 Sep 15;257:118116. doi: 10.1016/j.lfs.2020.118116. Epub 2020 Jul 
      20.