PMID- 32235767
OWN - NLM
STAT- MEDLINE
DCOM- 20210210
LR  - 20211204
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 9
IP  - 3
DP  - 2020 Mar 22
TI  - Pirfenidone Inhibits Cell Proliferation and Collagen I Production of Primary 
      Human Intestinal Fibroblasts.
LID - 10.3390/cells9030775 [doi]
LID - 775
AB  - Intestinal fibrosis is a common complication of inflammatory bowel disease. So 
      far, there is no safe and effective drug for intestinal fibrosis. Pirfenidone is 
      an anti-fibrotic compound available for the treatment of idiopathic pulmonary 
      fibrosis. Here, we explored the anti-proliferative and anti-fibrotic properties 
      of pirfenidone on primary human intestinal fibroblasts (p-hIFs). p-hIFs were 
      cultured in the absence and presence of pirfenidone. Cell proliferation was 
      measured by a real-time cell analyzer (xCELLigence) and BrdU incorporation. Cell 
      motility was monitored by live cell imaging. Cytotoxicity and cell viability were 
      analyzed by Sytox green, Caspase-3 and Water Soluble Tetrazolium Salt-1 (WST-1) 
      assays. Gene expression of fibrosis markers was determined by quantitative 
      reverse transcription PCR (RT-qPCR). The mammalian target of rapamycin (mTOR) 
      signaling was analyzed by Western blotting and type I collagen protein expression 
      additionally by immunofluorescence microscopy. Pirfenidone dose-dependently 
      inhibited p-hIF proliferation and motility, without inducing cell death. 
      Pirfenidone suppressed mRNA levels of genes that contribute to extracellular 
      matrix production, as well as basal and TGF-beta1-induced collagen I protein 
      production, which was associated with inhibition of the rapamycin-sensitive 
      mTOR/p70S6K pathway in p-hIFs. Thus, pirfenidone inhibits the proliferation of 
      intestinal fibroblasts and suppresses collagen I production through the 
      TGF-beta1/mTOR/p70S6K signaling pathway, which might be a novel and safe 
      anti-fibrotic strategy to treat intestinal fibrosis.
FAU - Cui, Yingying
AU  - Cui Y
AD  - Department of Gastroenterology and Hepatology, University Medical Center 
      Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
FAU - Zhang, Mengfan
AU  - Zhang M
AD  - Department of Gastroenterology and Hepatology, University Medical Center 
      Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
FAU - Leng, Changsen
AU  - Leng C
AD  - Department of Biomedical Sciences of Cells and Systems, section Molecular Cell 
      Biology, University Medical Center Groningen, University of Groningen, 9713 GZ 
      Groningen, The Netherlands.
FAU - Blokzijl, Tjasso
AU  - Blokzijl T
AD  - Department of Gastroenterology and Hepatology, University Medical Center 
      Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
AD  - Department of Laboratory Medicine, University Medical Center Groningen, 
      University of Groningen, 9713 GZ Groningen, The Netherlands.
FAU - Jansen, Bernadien H
AU  - Jansen BH
AD  - Department of Gastroenterology and Hepatology, University Medical Center 
      Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
FAU - Dijkstra, Gerard
AU  - Dijkstra G
AUID- ORCID: 0000-0003-4563-7462
AD  - Department of Gastroenterology and Hepatology, University Medical Center 
      Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
FAU - Faber, Klaas Nico
AU  - Faber KN
AD  - Department of Gastroenterology and Hepatology, University Medical Center 
      Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
AD  - Department of Laboratory Medicine, University Medical Center Groningen, 
      University of Groningen, 9713 GZ Groningen, The Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200322
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Collagen Type I)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Pyridones)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta1)
RN  - D7NLD2JX7U (pirfenidone)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
CIN - Cells. 2020 Jul 23;9(8):. PMID: 32717828
MH  - Cell Death/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Collagen Type I/*biosynthesis
MH  - Extracellular Matrix Proteins/metabolism
MH  - Fibroblasts/*cytology/drug effects/*metabolism
MH  - Humans
MH  - Intestines/*cytology
MH  - Phosphorylation/drug effects
MH  - Pyridones/*pharmacology
MH  - RNA, Messenger/genetics/metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Transforming Growth Factor beta1/pharmacology
PMC - PMC7140656
OTO - NOTNLM
OT  - TGF-beta1
OT  - collagen
OT  - fibroblast
OT  - inflammatory bowel disease
OT  - intestinal fibrosis
OT  - mTOR
OT  - pirfenidone
COIS- The authors declare no conflict of interest.
EDAT- 2020/04/03 06:00
MHDA- 2021/02/11 06:00
PMCR- 2020/03/01
CRDT- 2020/04/03 06:00
PHST- 2020/02/03 00:00 [received]
PHST- 2020/03/16 00:00 [revised]
PHST- 2020/03/20 00:00 [accepted]
PHST- 2020/04/03 06:00 [entrez]
PHST- 2020/04/03 06:00 [pubmed]
PHST- 2021/02/11 06:00 [medline]
PHST- 2020/03/01 00:00 [pmc-release]
AID - cells9030775 [pii]
AID - cells-09-00775 [pii]
AID - 10.3390/cells9030775 [doi]
PST - epublish
SO  - Cells. 2020 Mar 22;9(3):775. doi: 10.3390/cells9030775.