Hiwatashi Nao, Mukudai Shigeyuki, Bing Renjie, Branski Ryan C
Department of Otolaryngology-Head and Neck Surgery, New York University Voice Center, New York University School of Medicine, New York, New York, U.S.A.
Laryngoscope. 2018 Dec;128(12):E425-E428. doi: 10.1002/lary.27361. Epub 2018 Oct 16.
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.
In vitro.
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.
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).
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.
NA Laryngoscope, 128:E425-E428, 2018.
目的/假设：我们实验室最近将NR4A1描述为转化生长因子-β（TGF-β）诱导的声带（VF）纤维化的内源性抑制剂。我们之前的报告描述了NR4A1在体内VF愈合过程中的时间表达以及NR4A1敲低对体外成纤维细胞活性的影响。基于这些发现，我们推测NR4A1激动剂环孢菌素-B（Csn-B）可能具有显著的治疗潜力。
体外研究。
将人VF成纤维细胞暴露于TGF-β1和/或Csn-B中。对与纤维化相关的基因表达进行定量分析。此外，检测细胞收缩情况，作为我们细胞系中纤维化表型的替代指标。
正如预期的那样，TGF-β1刺激了COL1A1和ACTA2的表达。Csn-B显著下调了TGF-β1介导的这些基因的上调（分别为P = 0.009，P = 0.03）。Csn-B对与TGF-β/Smad信号通路相关的基因没有影响。Csn-B还降低了TGF-β1介导的我们细胞中的收缩表型（P = 0.004）。
NR4A1是声带纤维化的内源性抑制剂，而Csn-B作为NR4A1激动剂，可能会成为这种具有挑战性疾病的理想治疗候选药物。
NA 喉镜，128:E425-E428，2018年。
