PMID- 35309056
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220322
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 13
DP  - 2022
TI  - Inhibition of PI3K/AKT/mTOR Signalling Pathway Activates Autophagy and Suppresses 
      Peritoneal Fibrosis in the Process of Peritoneal Dialysis.
PG  - 778479
LID - 10.3389/fphys.2022.778479 [doi]
LID - 778479
AB  - Peritoneal dialysis (PD) is an important part of replacement therapy for kidney 
      failure. However, long-term PD treatment can cause peritoneal fibrosis. Autophagy 
      may be involved in the pathological mechanism of peritoneal fibrosis (PF). 
      Although autophagy is currently known to be involved in course of PF, its 
      specific effects still lack in-depth research. In this experiment, a high-glucose 
      (HG)-induced peritoneal fibrosis rat model was successfully established via 
      intraperitoneal injection of HG peritoneal dialysate, and the 
      phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and the mechanistic 
      target of rapamycin (mTOR) inhibitor rapamycin were used to treat peritoneal 
      fibrosis rats. In addition, in vitro studies of high glucose-induced peritoneal 
      fibrosis were performed using rat peritoneal mesothelial cells (PMCs). In vivo 
      and in vitro experiments showed that LY294002 and rapamycin effectively inhibited 
      the process of PF induced by high glucose. In addition, LY294002 and rapamycin 
      were found to alleviate fibrosis by eliminating intracellular reactive oxygen 
      species (ROS) levels, promoting the expression of the epithelial mesenchymal 
      transdifferentiation proteins zonula occludens-1 (ZO-1) and E-cadherin, and 
      inhibiting the expression of p-PI3K, PI3K, p-mTOR, mTOR, the fibroblast-specific 
      proteins ferroptosis suppressor protein 1 (FSP1), and alpha-smooth muscle actin 
      (alpha-SMA). Moreover, LY294002 and rapamycin promoted expression of 
      autophagy-related proteins LC3-II/I, p62, and beclin-1. The current data 
      indicated that inhibition of PI3K/AKT/mTOR signalling pathway activated autophagy 
      and suppressed PF in the process of PD. Therefore, intervention in this 
      signalling pathway may become a research goal for the prevention and treatment of 
      PF, which has important clinical significance.
CI  - Copyright (c) 2022 Jia, Qiu, Lin, Zhang, Li and Jin.
FAU - Jia, Miao
AU  - Jia M
AD  - Department of Nephrology, The People's Hospital of Suzhou New District, Suzhou, 
      China.
FAU - Qiu, Hong
AU  - Qiu H
AD  - Department of Nephrology, The People's Hospital of Suzhou New District, Suzhou, 
      China.
FAU - Lin, Lihua
AU  - Lin L
AD  - Department of Nephrology, The People's Hospital of Suzhou New District, Suzhou, 
      China.
FAU - Zhang, Shun
AU  - Zhang S
AD  - Department of Nephrology, The People's Hospital of Suzhou New District, Suzhou, 
      China.
FAU - Li, Damei
AU  - Li D
AD  - Department of Nephrology, The People's Hospital of Suzhou New District, Suzhou, 
      China.
FAU - Jin, Donghua
AU  - Jin D
AD  - Department of Nephrology, The People's Hospital of Suzhou New District, Suzhou, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20220304
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC8931542
OTO - NOTNLM
OT  - PI3K/AKT/mTOR signalling pathway
OT  - autophagy
OT  - peritoneal dialysis
OT  - peritoneal fibrosis
OT  - renal disease
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/03/22 06:00
MHDA- 2022/03/22 06:01
PMCR- 2022/03/04
CRDT- 2022/03/21 08:46
PHST- 2021/09/17 00:00 [received]
PHST- 2022/01/17 00:00 [accepted]
PHST- 2022/03/21 08:46 [entrez]
PHST- 2022/03/22 06:00 [pubmed]
PHST- 2022/03/22 06:01 [medline]
PHST- 2022/03/04 00:00 [pmc-release]
AID - 10.3389/fphys.2022.778479 [doi]
PST - epublish
SO  - Front Physiol. 2022 Mar 4;13:778479. doi: 10.3389/fphys.2022.778479. eCollection 
      2022.