PMID- 26192086
OWN - NLM
STAT- MEDLINE
DCOM- 20160105
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Linking)
VI  - 95
IP  - 10
DP  - 2015 Oct
TI  - Endoplasmic reticulum stress as a novel target to ameliorate 
      epithelial-to-mesenchymal transition and apoptosis of human peritoneal 
      mesothelial cells.
PG  - 1157-73
LID - 10.1038/labinvest.2015.91 [doi]
AB  - Epithelial-to-mesenchymal transition (EMT) and apoptosis of peritoneal 
      mesothelial cells are known to be the earliest mechanisms of peritoneal fibrosis 
      in peritoneal dialysis (PD). Endoplasmic reticulum (ER) stress with an unfolded 
      protein response is regarded to have a role in the development of organ fibrosis. 
      To investigate the potential role of ER stress as a target to prevent and/or 
      delay the development of peritoneal fibrosis, we examined the effect of ER stress 
      on EMT or apoptosis of human peritoneal mesothelial cells (HPMCs) and elucidated 
      the mechanisms underlying the protective effect of ER stress preconditioning on 
      TGF-beta1-induced EMT. ER stress inducers, tunicamycin (TM) and thapsigargin (TG), 
      induced EMT with Smad2/3 phosphorylation, an increased nuclear translocation of 
      beta-catenin and Snail expression. Low concentrations of TM and TG did not induce 
      apoptosis within 48 h; however, high concentrations of TM- (>1 ng/ml) and TG- 
      (>1 nM) induced apoptosis at 12 h with a persistent increase in C/EBP homologous 
      protein. TGF-beta1 induced EMT and apoptosis in HPMCs, which was ameliorated by 
      taurine-conjugated ursodeoxycholic acid, an ER stress blocker. Interestingly, 
      pre-treatment with TM or TG for 4 h also protected the cells from TGF-beta1-induced 
      EMT and apoptosis, demonstrating the role of ER stress as an adaptive response to 
      protect HPMCs from EMT and apoptosis. Peritoneal mesothelial cells isolated from 
      PD patients displayed an increase in GRP78/94, which was correlated with the 
      degree of EMT. These findings suggest that the modulation of ER stress in HPMCs 
      could serve as a novel approach to ameliorate peritoneal damage in PD patients.
FAU - Shin, Hyun-Soo
AU  - Shin HS
AD  - Department of Internal Medicine, Division of Nephrology, Ewha Medical Research 
      Center, School of Medicine, Ewha Womans University, Seoul, Republic of Korea.
FAU - Ryu, Eun-Sun
AU  - Ryu ES
AD  - Department of Internal Medicine, Division of Nephrology, Ewha Medical Research 
      Center, School of Medicine, Ewha Womans University, Seoul, Republic of Korea.
FAU - Oh, Eok-Soo
AU  - Oh ES
AD  - Department of Life Sciences, Division of Life and Pharmaceutical Sciences, Ewha 
      Womans University, Seoul, Republic of Korea.
FAU - Kang, Duk-Hee
AU  - Kang DH
AD  - Department of Internal Medicine, Division of Nephrology, Ewha Medical Research 
      Center, School of Medicine, Ewha Womans University, Seoul, Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150720
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (HSPA5 protein, human)
RN  - 0 (Membrane Transport Modulators)
RN  - 0 (Nuclear Localization Signals)
RN  - 0 (SMAD2 protein, human)
RN  - 0 (SMAD3 protein, human)
RN  - 0 (Smad2 Protein)
RN  - 0 (Smad3 Protein)
RN  - 0 (Snail Family Transcription Factors)
RN  - 0 (Transcription Factors)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (beta Catenin)
RN  - 11089-65-9 (Tunicamycin)
RN  - 67526-95-8 (Thapsigargin)
SB  - IM
MH  - Anti-Bacterial Agents/adverse effects
MH  - *Apoptosis
MH  - Ascitic Fluid/metabolism/pathology
MH  - Cells, Cultured
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - *Endoplasmic Reticulum Stress
MH  - *Epithelial-Mesenchymal Transition
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Membrane Transport Modulators/adverse effects
MH  - *Models, Biological
MH  - Nuclear Localization Signals/drug effects/metabolism
MH  - Peritoneal Dialysis/*adverse effects
MH  - Peritoneal Fibrosis/chemically induced/etiology/metabolism/*pathology
MH  - Phosphorylation/drug effects
MH  - Protein Processing, Post-Translational/drug effects
MH  - Smad2 Protein/metabolism
MH  - Smad3 Protein/metabolism
MH  - Snail Family Transcription Factors
MH  - Thapsigargin/adverse effects
MH  - Transcription Factors/genetics/metabolism
MH  - Transforming Growth Factor beta1/metabolism
MH  - Tunicamycin/adverse effects
MH  - *Unfolded Protein Response
MH  - beta Catenin/metabolism
EDAT- 2015/07/21 06:00
MHDA- 2016/01/06 06:00
CRDT- 2015/07/21 06:00
PHST- 2015/02/18 00:00 [received]
PHST- 2015/04/18 00:00 [revised]
PHST- 2015/05/12 00:00 [accepted]
PHST- 2015/07/21 06:00 [entrez]
PHST- 2015/07/21 06:00 [pubmed]
PHST- 2016/01/06 06:00 [medline]
AID - S0023-6837(22)01368-X [pii]
AID - 10.1038/labinvest.2015.91 [doi]
PST - ppublish
SO  - Lab Invest. 2015 Oct;95(10):1157-73. doi: 10.1038/labinvest.2015.91. Epub 2015 
      Jul 20.