PMID- 28352366
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220317
IS  - 1792-0981 (Print)
IS  - 1792-1015 (Electronic)
IS  - 1792-0981 (Linking)
VI  - 13
IP  - 2
DP  - 2017 Feb
TI  - Prolyl oligopeptidase attenuates hepatic stellate cell activation through 
      induction of Smad7 and PPAR-gamma.
PG  - 780-786
LID - 10.3892/etm.2017.4033 [doi]
AB  - Prolyl oligopeptidase (POP) is a serine endopeptidase widely distributed in vivo 
      with high activity in the liver. However, its biological functions in the liver 
      have remained largely elusive. A previous study by our group has shown that POP 
      produced N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) and thereby exerted an 
      anti-fibrogenic effect on hepatic stellate cells (HSCs) in vitro. It was 
      therefore hypothesized that POP may affect the activation state of HSCs and has 
      an important role in liver fibrosis. The HSC-T6 immortalized rat liver stellate 
      cell line was treated with the POP inhibitor S17092 or transfected with 
      recombinant lentivirus to overexpress POP. Cell proliferation and apoptosis were 
      determined using a Cell Counting Kit-8 and flow cytometry, respectively. The 
      activation status of HSCs was determined by examination of the expression of 
      alpha-smooth muscle actin (alpha-SMA), collagen I, monocyte chemoattractant protein-1 
      (MCP-1), transforming growth factor (TGF)-beta-Smad signaling and peroxisome 
      proliferator activated receptor-gamma (PPAR-gamma). Inhibition by S17092 decreased, 
      whereas lentiviral expression increased the activity of POP and cell 
      proliferation, while neither of the treatments affected cell apoptosis. Of note, 
      S17092 significantly increased, whereas POP overexpression decreased the 
      expression of alpha-SMA and MCP-1 without affecting the expression of collagen I and 
      TGF-beta1. Furthermore, S17092 caused a reduction, whereas POP overexpression caused 
      an upregulation of Smad7 protein and PPAR-gamma, but not phosphorylated-Smad2/3 
      expression. In conclusion, POP attenuated the activation of HSCs through 
      inhibition of TGF-beta signaling and induction of PPAR-gamma, which may have therapeutic 
      potential in liver fibrosis.
FAU - Zhou, Da
AU  - Zhou D
AD  - Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University 
      School of Medicine, Shanghai 200092, P.R. China.
FAU - Wang, Jing
AU  - Wang J
AD  - Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University 
      School of Medicine, Shanghai 200092, P.R. China.
FAU - He, Ling-Nan
AU  - He LN
AD  - Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University 
      School of Medicine, Shanghai 200092, P.R. China.
FAU - Li, Bing-Hang
AU  - Li BH
AD  - Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University 
      School of Medicine, Shanghai 200092, P.R. China.
FAU - Ding, Yong-Nian
AU  - Ding YN
AD  - Department of Gastroenterology, The Second Affiliated Hospital of Xinjiang 
      Medical University, Urumqi, Xinjiang 830028, P.R. China.
FAU - Chen, Yuan-Wen
AU  - Chen YW
AD  - Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University 
      School of Medicine, Shanghai 200092, P.R. China.
FAU - Fan, Jian-Gao
AU  - Fan JG
AD  - Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University 
      School of Medicine, Shanghai 200092, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20170105
PL  - Greece
TA  - Exp Ther Med
JT  - Experimental and therapeutic medicine
JID - 101531947
PMC - PMC5348651
OTO - NOTNLM
OT  - hepatic stellate cells
OT  - peroxisome proliferator activated receptor-gamma
OT  - prolyl oligopeptidase
OT  - transforming growth factor-beta-Smad signaling
EDAT- 2017/03/30 06:00
MHDA- 2017/03/30 06:01
PMCR- 2017/01/05
CRDT- 2017/03/30 06:00
PHST- 2015/07/22 00:00 [received]
PHST- 2016/10/21 00:00 [accepted]
PHST- 2017/03/30 06:00 [entrez]
PHST- 2017/03/30 06:00 [pubmed]
PHST- 2017/03/30 06:01 [medline]
PHST- 2017/01/05 00:00 [pmc-release]
AID - ETM-0-0-4033 [pii]
AID - 10.3892/etm.2017.4033 [doi]
PST - ppublish
SO  - Exp Ther Med. 2017 Feb;13(2):780-786. doi: 10.3892/etm.2017.4033. Epub 2017 Jan 
      5.