PMID- 27181436
OWN - NLM
STAT- MEDLINE
DCOM- 20170606
LR  - 20220408
IS  - 1502-7708 (Electronic)
IS  - 0036-5521 (Linking)
VI  - 51
IP  - 11
DP  - 2016 Nov
TI  - Pirfenidone inhibits the proliferation of fibroblasts from patients with active 
      Crohn's disease.
PG  - 1321-5
LID - 10.1080/00365521.2016.1185146 [doi]
AB  - OBJECTIVE: One-third of Crohn's disease (CD) patients develop intestinal 
      strictures that require repeated surgical intervention. Current anti-inflammatory 
      therapies have limited effect on stricture development, which necessitates the 
      exploration of new pharmacological approaches. Pirfenidone (PFD), a novel 
      anti-fibrotic agent, was recently approved in Europe for the treatment of 
      idiopathic pulmonary fibrosis (IPF). We hypothesized that observations in IPF 
      could be transferable to intestinal fibrosis and that PFD inhibits the 
      proliferation and extracellular matrix (ECM) turnover of gut-derived fibroblasts 
      from CD patients. MATERIAL AND METHODS: Fibroblasts were isolated from biopsies 
      of inflamed (n = 8) and non-inflamed (n = 5) colonic mucosa. Expression of CD90 
      and alpha-smooth muscle actin (alphaSMA) expression was determined by flow cytometry. 
      The fibroblasts were cultured with PFD (0.5, 1.0 and 2.0 mg/ml). Proliferation 
      was evaluated with CellTiter 96((R)) AQueous One Solution Cell Proliferation Assay. 
      Production of matrix metalloproteinase-3 (MMP-3), tissue inhibitor of 
      metalloproteinases-1 (TIMP-1) and collagen were assessed using ELISA and 
      calorimetric assays, respectively. RESULTS: The majority of the fibroblasts were 
      alphaSMA-positive myofibroblasts. PFD inhibited fibroblast proliferation [0.94 (PFD 
      0.5 mg/ml); 0.76 (1.0 mg/ml); 0.58 (2.0 mg/ml)] and production of MMP-3 [0.85 
      (0.5 mg/ml); 0.74 (1.0 mg/ml); 0.63 (2.0 mg/ml)] dose-dependently (both 
      p = 0.0001). The anti-proliferative effect of PFD was reversible (p = 0.0001), 
      indicating that PFD does not act by an irreversible cytotoxic mechanism. PFD did 
      not influence neither TIMP-1 nor collagen production. CONCLUSION: PFD inhibited 
      the proliferation and the production of MMP-3 dose-dependently in gut-derived 
      fibroblast from CD patients. Our observations support further studies on PFD in 
      stricturing CD.
FAU - Kadir, Sara-Irini
AU  - Kadir SI
AD  - a Department of Hepatology and Gastroenterology , Gastro-Immuno Research 
      Laboratory (GIRL), Aarhus University Hospital , Aarhus , Denmark ;
FAU - Wenzel Kragstrup, Tue
AU  - Wenzel Kragstrup T
AD  - b Department of Biomedicine , Aarhus University , Aarhus , Denmark.
FAU - Dige, Anders
AU  - Dige A
AD  - a Department of Hepatology and Gastroenterology , Gastro-Immuno Research 
      Laboratory (GIRL), Aarhus University Hospital , Aarhus , Denmark ;
FAU - Kok Jensen, Simon
AU  - Kok Jensen S
AD  - b Department of Biomedicine , Aarhus University , Aarhus , Denmark.
FAU - Dahlerup, Jens Frederik
AU  - Dahlerup JF
AD  - a Department of Hepatology and Gastroenterology , Gastro-Immuno Research 
      Laboratory (GIRL), Aarhus University Hospital , Aarhus , Denmark ;
FAU - Kelsen, Jens
AU  - Kelsen J
AD  - a Department of Hepatology and Gastroenterology , Gastro-Immuno Research 
      Laboratory (GIRL), Aarhus University Hospital , Aarhus , Denmark ;
LA  - eng
PT  - Journal Article
DEP - 20160516
PL  - England
TA  - Scand J Gastroenterol
JT  - Scandinavian journal of gastroenterology
JID - 0060105
RN  - 0 (ACTA2 protein, human)
RN  - 0 (Actins)
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Pyridones)
RN  - 0 (TIMP1 protein, human)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 9007-34-5 (Collagen)
RN  - D7NLD2JX7U (pirfenidone)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Actins/metabolism
MH  - Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use
MH  - Cell Proliferation/*drug effects
MH  - Cells, Cultured
MH  - Collagen/metabolism
MH  - Crohn Disease/*drug therapy/pathology
MH  - Denmark
MH  - Endoscopy
MH  - Female
MH  - Fibroblasts/*cytology/metabolism
MH  - Fibrosis
MH  - Humans
MH  - Intestinal Mucosa/pathology
MH  - Linear Models
MH  - Male
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Pyridones/*therapeutic use
MH  - Tissue Inhibitor of Metalloproteinase-1/metabolism
OTO - NOTNLM
OT  - Crohn's disease
OT  - fibrosis
OT  - pirfenidone
EDAT- 2016/05/18 06:00
MHDA- 2017/06/07 06:00
CRDT- 2016/05/17 06:00
PHST- 2016/05/17 06:00 [entrez]
PHST- 2016/05/18 06:00 [pubmed]
PHST- 2017/06/07 06:00 [medline]
AID - 10.1080/00365521.2016.1185146 [doi]
PST - ppublish
SO  - Scand J Gastroenterol. 2016 Nov;51(11):1321-5. doi: 
      10.1080/00365521.2016.1185146. Epub 2016 May 16.