Premium
Potential treatment for vocal fold scar with pirfenidone
Author(s) -
Kodama Haruka,
Kumai Yoshihiko,
Nishimoto Kohei,
Toya Yutaka,
Miyamaru Satoru,
Furushima Shinobu,
Yumoto Eiji
Publication year - 2018
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1002/lary.26999
Subject(s) - pirfenidone , smad , immunohistochemistry , vocal folds , messenger rna , transforming growth factor , idiopathic pulmonary fibrosis , contraction (grammar) , fibrosis , pulmonary fibrosis , medicine , microbiology and biotechnology , chemistry , andrology , pathology , biology , anatomy , lung , biochemistry , gene , larynx
Objectives/Hypothesis Pirfenidone (PFD) is a strong antifibrotic agent that has been clinically approved in Japan for idiopathic pulmonary fibrosis. We examined the antifibrotic effects of PFD on fibroblasts isolated from scarred vocal folds (VFs) of ferrets in vitro. Study Design Prospective animal experiments with controls. Methods Scar fibroblasts (SFs) were isolated from scarred VFs that had been electrocauterized 2 weeks before harvesting (N = 4). Normal fibroblasts (NFs) were isolated from intact VFs (N = 4). SFs and NFs were incubated in the presence of 10 ng/mL transforming growth factor β1 (TGF‐β1), with or without PFD. After the 48‐hour incubation, mRNA expression levels of α smooth muscle actin (αSMA), TGF‐β1, collagen type I, and hyaluronan synthase 2 (HAS2) were examined by real‐time polymerase chain reaction. Immunohistochemistry with anti‐αSMA anti‐collagen type I and phosphorylated Smad (p‐Smad)2/3 antibodies in SFs with or without PFD was performed. SFs and NFs were cultured in collagen gel with or without PFD for 48 hours, and the extent of gel contraction was examined quantitatively. Results PFD treatment significantly ( P < .05) decreased mRNA expression of collagen type I, significantly increased mRNA expression of TGF‐β1 and HAS2, and significantly suppressed collagen gel contraction. However, it did not have a significant effect on the expression of αSMA. The expression of p‐Smad2/3 in the nucleus was faded with PFD, possibly demonstrating the suppression of translocation of p‐Smad2/3 from cytoplasm to nucleus with PFD. Conclusions This is the first report to demonstrate the in vitro antifibrotic effects of PFD on fibroblasts isolated from scarred VFs of ferrets. Level of Evidence NA. Laryngoscope , 128:E171–E177, 2018