PMID- 32949996
OWN - NLM
STAT- MEDLINE
DCOM- 20210719
LR  - 20211204
IS  - 2352-3964 (Electronic)
IS  - 2352-3964 (Linking)
VI  - 60
DP  - 2020 Oct
TI  - Autophagy induction promotes renal cyst growth in polycystic kidney disease.
PG  - 102986
LID - S2352-3964(20)30362-5 [pii]
LID - 10.1016/j.ebiom.2020.102986 [doi]
LID - 102986
AB  - BACKGROUND: Polycystic kidney disease (PKD) involves renal cysts arising from 
      proliferating tubular cells. Autophagy has been recently suggested as a potential 
      therapeutic target in PKD, and mammalian target of rapamycin (mTOR) is a key 
      negative regulator of autophagy. However, the effect of autophagy regulation on 
      cystogenesis has not been elucidated in PKD mice. METHODS: Clinical validation 
      was performed using GEO datasets and autosomal dominant polycystic kidney disease 
      (ADPKD) patient samples. Newly established PKD and LC3 transgenic mice were used 
      for in vivo verifications, and additional tests were performed in vitro and in 
      vivo using multiple autophagy drugs. FINDINGS: Neither autophagy stimulation nor 
      LC3 overexpression alleviated PKD. Furthermore, we observed the inhibitory effect 
      of an autophagy inhibitor on cysts, indicating its possible therapeutic use in a 
      specific group of patients with ADPKD. INTERPRETATION: Our findings provide a 
      novel insight into the pathogenesis related to autophagy in PKD, suggesting that 
      drugs related to autophagy regulation should be considered with caution for 
      treating PKD. FUNDING SOURCES: This work was supported by grants from the Bio & 
      Medical Technology Development Program; the Collaborative Genome Program for 
      Fostering New Post-Genome Industry of the NRF; the Basic Science Program.
CI  - Copyright (c) 2020 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Lee, Eun Ji
AU  - Lee EJ
AD  - Department of Biological Science, Sookmyung Women's University, Seoul 04310, 
      Republic of Korea.
FAU - Ko, Je Yeong
AU  - Ko JY
AD  - Department of Biological Science, Sookmyung Women's University, Seoul 04310, 
      Republic of Korea.
FAU - Oh, Sumin
AU  - Oh S
AD  - Department of Biological Science, Sookmyung Women's University, Seoul 04310, 
      Republic of Korea.
FAU - Jun, Jaehee
AU  - Jun J
AD  - Department of Biological Science, Sookmyung Women's University, Seoul 04310, 
      Republic of Korea.
FAU - Mun, Hyowon
AU  - Mun H
AD  - Department of Biological Science, Sookmyung Women's University, Seoul 04310, 
      Republic of Korea.
FAU - Lim, Chae Ji
AU  - Lim CJ
AD  - Department of Biology, Ewha Womans University, Seoul 03760, Republic of Korea.
FAU - Seo, Seungwoon
AU  - Seo S
AD  - Department of Biology, Ewha Womans University, Seoul 03760, Republic of Korea.
FAU - Ko, Hyuk Wan
AU  - Ko HW
AD  - Department of Biochemistry, Yonsei University, Seoul 03722, Republic of Korea.
FAU - Kim, Hyunho
AU  - Kim H
AD  - Center for Medical Innovation, Biomedical Research Institute, Seoul National 
      University Hospital, Seoul 03082, Republic of Korea.
FAU - Oh, Yun Kyu
AU  - Oh YK
AD  - Department of Internal Medicine, Seoul National University Boramae Medical 
      Center, Seoul 07061, Republic of Korea.
FAU - Ahn, Curie
AU  - Ahn C
AD  - Department of Internal Medicine, Seoul National University College of Medicine, 
      Seoul 03080, Republic of Korea.
FAU - Kang, Minyong
AU  - Kang M
AD  - Department of Urology, Samsung Medical Center, Sungkyunkwan University School of 
      Medicine, Seoul 06351, Republic of Korea.
FAU - Kim, Min Jung
AU  - Kim MJ
AD  - Department of Biological Science, Sookmyung Women's University, Seoul 04310, 
      Republic of Korea.
FAU - Yoo, Kyung Hyun
AU  - Yoo KH
AD  - Department of Biological Science, Sookmyung Women's University, Seoul 04310, 
      Republic of Korea.
FAU - Oh, Goo Taeg
AU  - Oh GT
AD  - Department of Biology, Ewha Womans University, Seoul 03760, Republic of Korea. 
      Electronic address: gootaeg@ewha.ac.kr.
FAU - Park, Jong Hoon
AU  - Park JH
AD  - Department of Biological Science, Sookmyung Women's University, Seoul 04310, 
      Republic of Korea. Electronic address: parkjh@sookmyung.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20200916
PL  - Netherlands
TA  - EBioMedicine
JT  - EBioMedicine
JID - 101647039
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - *Autophagy/genetics
MH  - Cell Line
MH  - Computational Biology
MH  - Cysts/*pathology
MH  - Disease Models, Animal
MH  - Disease Susceptibility
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Gene Expression Profiling
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - Phosphorylation
MH  - Polycystic Kidney Diseases/*etiology/metabolism/*pathology
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Zebrafish
PMC - PMC7501056
OTO - NOTNLM
OT  - Autophagy
OT  - Ift46
OT  - PKD
OT  - Polycystic kidney
COIS- Declaration of Competing Interest J.H. Park, G.T. Oh and J.Y. Ko have filed a 
      patent in South Korea for the establishment of the Ift46-deleted model (patent 
      number: 10-1618124). The others have nothing to disclose.
EDAT- 2020/09/20 06:00
MHDA- 2021/07/20 06:00
PMCR- 2020/09/16
CRDT- 2020/09/19 20:19
PHST- 2020/07/18 00:00 [received]
PHST- 2020/08/14 00:00 [revised]
PHST- 2020/08/19 00:00 [accepted]
PHST- 2020/09/20 06:00 [pubmed]
PHST- 2021/07/20 06:00 [medline]
PHST- 2020/09/19 20:19 [entrez]
PHST- 2020/09/16 00:00 [pmc-release]
AID - S2352-3964(20)30362-5 [pii]
AID - 102986 [pii]
AID - 10.1016/j.ebiom.2020.102986 [doi]
PST - ppublish
SO  - EBioMedicine. 2020 Oct;60:102986. doi: 10.1016/j.ebiom.2020.102986. Epub 2020 Sep 
      16.