Next Article in Journal
Graphene Oxide Nanosheets for Localized Hyperthermia—Physicochemical Characterization, Biocompatibility, and Induction of Tumor Cell Death
Previous Article in Journal
Lamin A and Prelamin a Counteract Migration of Osteosarcoma Cells
Open AccessArticle

Pirfenidone Inhibits Cell Proliferation and Collagen I Production of Primary Human Intestinal Fibroblasts

1
Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
2
Department of Biomedical Sciences of Cells and Systems, section Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
3
Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Cells 2020, 9(3), 775; https://doi.org/10.3390/cells9030775
Received: 3 February 2020 / Revised: 16 March 2020 / Accepted: 20 March 2020 / Published: 22 March 2020
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-β1-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-β1/mTOR/p70S6K signaling pathway, which might be a novel and safe anti-fibrotic strategy to treat intestinal fibrosis. View Full-Text
Keywords: intestinal fibrosis; pirfenidone; mTOR; TGF-β1; collagen; fibroblast; inflammatory bowel disease intestinal fibrosis; pirfenidone; mTOR; TGF-β1; collagen; fibroblast; inflammatory bowel disease
Show Figures

Figure 1

MDPI and ACS Style

Cui, Y.; Zhang, M.; Leng, C.; Blokzijl, T.; Jansen, B.H.; Dijkstra, G.; Faber, K.N. Pirfenidone Inhibits Cell Proliferation and Collagen I Production of Primary Human Intestinal Fibroblasts. Cells 2020, 9, 775.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop