Pirfenidone suppresses keloid fibroblast-embedded collagen gel contraction.
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.
Department of Dermatology, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan.
Masuyoshi
M
Saito
Masashi
M
Yamazaki
Tatsuo
T
Maeda
Hajime
H
Matsumura
Yasuhiro
Y
Setoguchi
Ryoji
R
Tsuboi
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism*; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D005782:Gels / Q000378:metabolism; D006801:Humans; D007627:Keloid / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D011728:Pyridones / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D024042:Collagen Type I; D005782:Gels; D011728:Pyridones; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; C093844:pirfenidone