PMID- 31881325
OWN - NLM
STAT- MEDLINE
DCOM- 20210609
LR  - 20210609
IS  - 1873-3913 (Electronic)
IS  - 0898-6568 (Print)
IS  - 0898-6568 (Linking)
VI  - 68
DP  - 2020 Apr
TI  - Apoptosis and autophagy in polycystic kidney disease (PKD).
PG  - 109518
LID - S0898-6568(19)30314-6 [pii]
LID - 10.1016/j.cellsig.2019.109518 [doi]
AB  - Apoptosis in the cystic epithelium is observed in most rodent models of 
      polycystic kidney disease (PKD) and in human autosomal dominant PKD (ADPKD). 
      Apoptosis inhibition decreases cyst growth, whereas induction of apoptosis in the 
      kidney of Bcl-2 deficient mice increases proliferation of the tubular epithelium 
      and subsequent cyst formation. However, alternative evidence indicates that both 
      induction of apoptosis as well as increased overall rates of apoptosis are 
      associated with decreased cyst growth. Autophagic flux is suppressed in cell, 
      zebra fish and mouse models of PKD and suppressed autophagy is known to be 
      associated with increased apoptosis. There may be a link between apoptosis and 
      autophagy in PKD. The mammalian target of rapamycin (mTOR), B-cell lymphoma 2 
      (Bcl-2) and caspase pathways that are known to be dysregulated in PKD, are also 
      known to regulate both autophagy and apoptosis. Induction of autophagy in cell 
      and zebrafish models of PKD results in suppression of apoptosis and reduced cyst 
      growth supporting the hypothesis autophagy induction may have a therapeutic role 
      in decreasing cyst growth, perhaps by decreasing apoptosis and proliferation in 
      PKD. Future research is needed to evaluate the effects of direct autophagy 
      inducers on apoptosis in rodent PKD models, as well as the cause and effect 
      relationship between autophagy, apoptosis and cyst growth in PKD.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Nowak, Kristen L
AU  - Nowak KL
AD  - Division of Renal Diseases and Hypertension, Univ. of Colorado Anschutz Medical 
      Campus, Aurora, CO, USA.
FAU - Edelstein, Charles L
AU  - Edelstein CL
AD  - Division of Renal Diseases and Hypertension, Univ. of Colorado Anschutz Medical 
      Campus, Aurora, CO, USA. Electronic address: Charles.edelstein@cuanschutz.edu.
LA  - eng
GR  - I01 BX003803/BX/BLRD VA/United States
GR  - K01 DK103678/DK/NIDDK NIH HHS/United States
GR  - P30 DK090868/DK/NIDDK NIH HHS/United States
GR  - R03 DK118215/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Review
DEP - 20191224
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Caspase Inhibitors)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - *Autophagy
MH  - Caspase Inhibitors/pharmacology
MH  - Caspases/metabolism
MH  - Humans
MH  - Polycystic Kidney Diseases/*pathology/therapy
MH  - Signal Transduction
PMC - PMC7127985
MID - NIHMS1067050
OTO - NOTNLM
OT  - Apoptosis
OT  - Autophagy
OT  - Polycystic kidney disease
EDAT- 2019/12/28 06:00
MHDA- 2021/06/10 06:00
PMCR- 2021/04/01
CRDT- 2019/12/28 06:00
PHST- 2019/09/27 00:00 [received]
PHST- 2019/12/20 00:00 [revised]
PHST- 2019/12/21 00:00 [accepted]
PHST- 2019/12/28 06:00 [pubmed]
PHST- 2021/06/10 06:00 [medline]
PHST- 2019/12/28 06:00 [entrez]
PHST- 2021/04/01 00:00 [pmc-release]
AID - S0898-6568(19)30314-6 [pii]
AID - 10.1016/j.cellsig.2019.109518 [doi]
PST - ppublish
SO  - Cell Signal. 2020 Apr;68:109518. doi: 10.1016/j.cellsig.2019.109518. Epub 2019 
      Dec 24.