The effects of cytosporone‐B, a novel antifibrotic agent, on vocal fold fibroblasts

• Published in: The Laryngoscope 2018-12, Vol.128 (12), p.E425-E428
• Main Authors: Hiwatashi, Nao, Mukudai, Shigeyuki, Bing, Renjie, Branski, Ryan C.
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Cell Differentiation; Cell Line; Collagen - drug effects; Collagen Type I - metabolism; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibrosis; Humans; NR4A1; nuclear receptor; Nuclear Receptor Subfamily 4, Group A, Member 1 - agonists; Nuclear Receptor Subfamily 4, Group A, Member 1 - metabolism; Phenylacetates - metabolism; Phenylacetates - pharmacology; Transforming Growth Factor beta1 - metabolism; Transforming Growth Factor beta1 - pharmacology; transforming growth factor‐β; Vocal Cords - cytology; Vocal Cords - pathology; Vocal fold; voice
• ISSN: 0023-852X; 1531-4995
• DOI: 10.1002/lary.27361

Objectives/Hypothesis Our laboratory recently described NR4A1 as an endogenous inhibitor of TGF‐β–induced vocal fold (VF) fibrosis. Our prior report described the temporal expression of NR4A1 during VF healing in vivo and the effects of NR4A1 knockdown on fibroplastic cell activities in vitro. Based on these findings, we hypothesized that cytosporone‐B (Csn‐B), an NR4A1 agonist, may hold significant therapeutic potential. Study Design In vitro. Methods Human VF fibroblasts were exposed to TGF‐β1+/‐Csn‐B. Expression of genes related to fibrosis were quantified. In addition, contraction was assayed as a surrogate for the fibrotic phenotype in our cell line. Results TGF‐B1 stimulated COL1A1 and ACTA2, as expected. Csn‐B significantly downregulated TGF‐β1–mediated upregulation of these genes (P = .009, P = .03, respectively). Csn‐B had no effect on genes related to TGF‐β/Smad signaling. Csn‐B also decreased the TGF‐β1–mediated contractile phenotype in our cells (P = .004). Conclusions NR4A1 is an endogenous inhibitor of fibrosis in the vocal folds and Csn‐B, as an NR4A1 agonist, may evolve as an ideal, therapeutic candidate for this challenging condition. Level of Evidence NA Laryngoscope, 128:E425–E428, 2018