A Controlled Clinical Trial With Pirfenidone in the Treatment of Pathological Skin Scarring Caused by Burns in Pediatric Patients

Armendáriz‐Borunda, Juan; Lyra-González, Iván; Medina-Preciado, David; González‐García, Ignacio; Martinez-Fong, Daniel; Miranda, Rodolfo Ariel; Magaña-Castro, Rogelio; Peña-Santoyo, Pedro; García-Rocha, Sergio; Bautista, Carlos Alfredo; Godoy, Jesús Armando Sánchez; Flores-Montana, Jesus; Floresvillar-Mosqueda, Jorge; Armendariz-Vazquez, Oscar; Lucano-Landeros, Martha Silvia; Mercado, Mónica Vázquez-Del; Sánchez-Parada, María Guadalupe

doi:10.1097/sap.0b013e31821b6d08

Cited by 43 publications

(20 citation statements)

References 48 publications

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“…However, the injection of triamcinolone was more effective using this model [29]. Recently, topical application of pirfenidone has been tested to treat burns in children, with the result that 8% pirfenidone gel 3 times a day was found to be more effective and safer for the treatment of hypertrophic scars caused by burns, as compared with standard pressure therapy [3].…”

Section: Discussionmentioning

confidence: 97%

“…It inhibits the heat shock protein (HSP) 47 expression induced by TGFb1 in human lung fibroblasts [22], and has also been therapeutically used for idiopathic pulmonary fibrosis (IPF) [4,25,27]. In one journal of plastic surgery, topical application of pirfenidone was claimed to be efficacious for the treatment of hypertrophic scars [3]. However, no other reports on the clinical application of pirfenidone have been published in dermatology.…”

Section: Introductionmentioning

confidence: 98%

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Pirfenidone suppresses keloid fibroblast-embedded collagen gel contraction

et al. 2011

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Keloid is a clinically intractable disease that causes disfigurement, itching, and pain due to abnormal proliferation of fibroblasts and production of collagen. Pirfenidone is a novel anti-fibrotic agent that inhibits the progression of fibrosis occurring in the keloid lesions of the lung and kidney. In order to examine whether pirfenidone has a therapeutic effect on keloid lesions, we prepared an in vitro wound contraction model with keloid fibroblasts. The gel contractility of a mixture of keloid fibroblasts and an acid-soluble collagen solution was examined with/without transforming growth factor (TGF)-β1 in the presence or absence of pirfenidone. Real time RT-PCR was performed to detect mRNA expression of TGFB1, CTGF, aSMA, and Col1A1 quantitatively in keloid fibroblasts incubated with/without TGF-β1 in the presence or absence of pirfenidone. The contractility of keloid fibroblast-embedded collagen gel was increased after the addition of TGF-β1. Pirfenidone suppressed gel contraction with TGF-β1 dose dependently. TGF-β1 stimulated mRNA expression of TGFB1, CTGF, aSMA, and Col1A1 in keloid fibroblasts, while pirfenidone significantly inhibited mRNA expression of CTGF and aSMA in the identical cells. These findings suggest that pirfenidone suppresses the contraction of keloid-derived fibroblasts by inhibiting the down-stream pathway of TGF-β1, thus demonstrating its therapeutic utility for the treatment of keloid lesions.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 98%

Pirfenidone suppresses keloid fibroblast-embedded collagen gel contraction

et al. 2011

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“…In the present study, we have chosen to investigate the action of pirfenidone (PFD; 5-methyl-1-phenyl-2(1H)-pyridone) a small molecule well-documented for its antifibrotic and anti-inflammatory properties in a variety of pre-clinical and in vitro models in different organs, including fibrosis of the lung [23], kidney [24], heart [25], liver [26], and skin [27]. PFD has been shown to inhibit both production and activity of TGF-β1, a cytokine that stimulates collagen synthesis and inhibits its degradation [28], and also to reduce the production of other fibrogenesis mediators, such as fibronectin and connective tissue growth factor (CTGF) [29, 30].…”

Section: Introductionmentioning

confidence: 99%

Anti-fibrotic action of pirfenidone in Dupuytren’s disease-derived fibroblasts

Zhou

Liu

Gallo

et al. 2016

BMC Musculoskelet Disord

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BackgroundDupuytren’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.MethodsFibroblasts 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.ResultsOur 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.ConclusionTaken 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.

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“…It exhibits well-documented antifibrotic and anti-inflammatory properties in a variety of animal and in vitro models in different organs, including fibrosis of the lung, 17 kidneys, 18 heart, 19 liver, 20 and skin. 21 The exact molecular mechanism of action so far is unknown. 22 Pirfenidone influences significantly the production of various cytokines and growth factors, with the most commonly reported effect being a reduction of transforming growth factor-b (TGF-b).…”

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confidence: 99%

Decreased Fibrogenesis After Treatment with Pirfenidone in a Newly Developed Mouse Model of Intestinal Fibrosis

Meier

Lutz

Cosín-Roger

et al. 2016

Inflammatory Bowel Diseases

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BACKGROUND Fibrosis as a common problem in patients with Crohn's disease is a result of an imbalance toward excessive tissue repair. At present, there is no specific treatment option. Pirfenidone is approved for the treatment of idiopathic pulmonary fibrosis with both antifibrotic and anti-inflammatory effects. We subsequently investigated the impact of pirfenidone treatment on development of fibrosis in a new mouse model of intestinal fibrosis. METHODS Small bowel resections from donor mice were transplanted subcutaneously into the neck of recipients. Animals received either pirfenidone (100 mg/kg, three times daily, orally) or vehicle. RESULTS After administration of pirfenidone, a significantly decreased collagen layer thickness was revealed as compared to vehicle (9.7 ± 1.0 versus 13.5 ± 1.5 µm, respectively, **P < 0.001). Transforming growth factor-and matrix metalloproteinase-9 were significantly decreased after treatment with pirfenidone as confirmed by real-time PCR (0.42 ± 0.13 versus 1.00 ± 0.21 and 0.46 ± 0.24 versus 1.00 ± 0.62 mRNA expression level relative to GAPDH, respectively, *P < 0.05). Significantly decreased transforming growth factor-after administration of pirfenidone was confirmed by Western blotting. CONCLUSION In our mouse model, intestinal fibrosis can be reliably induced and is developed within 7 days. Pirfenidone partially prevented the development of fibrosis, making it a potential treatment option against Crohn's disease-associated fibrosis.

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A Controlled Clinical Trial With Pirfenidone in the Treatment of Pathological Skin Scarring Caused by Burns in Pediatric Patients

Abstract: Topical administration of 8% PFD gel 3 times a day is more effective and safe in the treatment of hypertrophic scars caused by burns in children, as compared with standard pressure therapy.

Cited by 43 publications

References 48 publications

Pirfenidone suppresses keloid fibroblast-embedded collagen gel contraction

Pirfenidone suppresses keloid fibroblast-embedded collagen gel contraction

Anti-fibrotic action of pirfenidone in Dupuytren’s disease-derived fibroblasts

Decreased Fibrogenesis After Treatment with Pirfenidone in a Newly Developed Mouse Model of Intestinal Fibrosis

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