Title |
Anti-fibrotic action of pirfenidone in Dupuytren’s disease-derived fibroblasts
|
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Published in |
BMC Musculoskeletal Disorders, November 2016
|
DOI | 10.1186/s12891-016-1326-y |
Pubmed ID | |
Authors |
Chaoming Zhou, Fang Liu, Phillip H. Gallo, Mark E. Baratz, Sandeep Kathju, Latha Satish |
Abstract |
Dupuytren's disease (DD) is a complex fibro-proliferative disorder of the hand that is often progressive and eventually can cause contractures of the affected fingers. Transforming growth factor beta (TGF-β1) has been implicated as a key stimulator of myofibroblast activity and fascial contraction in DD. Pirfenidone (PFD) is an active small molecule shown to inhibit TGF-β1-mediated action in other fibrotic disorders. This study investigates the efficacy of PFD in vitro in inhibiting TGF-β1-mediated cellular functions leading to Dupuytren's fibrosis. Fibroblasts harvested from (DD) and carpal tunnel (CT)- tissues were treated with or without TGF-β1 and/or PFD and were subjected to cell migration, cell proliferation and cell contraction assays. ELISA; western blots and real time RT-PCR assays were performed to determine the levels of fibronectin; p-Smad2/Smad3; alpha-smooth muscle actin (α-SMA), α2 chain of type I collagen and α1 chain of type III collagen respectively. Our results show that PFD effectively inhibits TGF-β1-induced cell migration, proliferation and cell contractile properties of both CT- and DD-derived fibroblasts. TGF-β1-induced α-SMA mRNA and protein levels were inhibited at the higher concentration of PFD (800 μg/ml). Interestingly, TGF-β1 induction of type I and type III collagens and fibronectin was inhibited by PFD in both CT- and DD- derived fibroblasts, but the effect was more prominent in DD cells. PFD down-regulated TGF-β1-induced phosphorylation of Smad2/Smad3, a key factor in the TGF-β1 signaling pathway. Taken together these results suggest the PFD can potentially prevent TGF-β1-induced fibroblast to myofibroblast transformation and inhibit ECM production mainly Type I- and Type III- collagen and fibronectin in DD-derived fibroblasts. Further in-vivo studies with PFD may lead to a novel therapeutic application in preventing the progression or recurrence of Dupuytren's disease. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 30 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 7 | 23% |
Professor > Associate Professor | 4 | 13% |
Student > Ph. D. Student | 4 | 13% |
Other | 3 | 10% |
Student > Bachelor | 3 | 10% |
Other | 4 | 13% |
Unknown | 5 | 17% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 12 | 40% |
Biochemistry, Genetics and Molecular Biology | 6 | 20% |
Agricultural and Biological Sciences | 2 | 7% |
Immunology and Microbiology | 2 | 7% |
Social Sciences | 1 | 3% |
Other | 1 | 3% |
Unknown | 6 | 20% |