Effects of Transforming Growth Factor-β1 on Human Vocal Fold Fibroblasts
Effects of Transforming Growth Factor-β1 on Human Vocal Fold Fibroblasts
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DOI：
10.1177/000348940911800310
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发表时间：
2009-03-01
影响因子：
1.4
通讯作者：
Felsen, Diane
中科院分区：
文献类型：
--
作者：
Branski, Ryan C.;Barbieri, Silvia S.;Felsen, Diane
目的：我们研究了转化生长因子（TGF）-β对永生化人声带成纤维细胞的影响。方法：正常人声带成纤维细胞进行连续的慢病毒转导与人类端粒酶（hTERT）和SV 40大T抗原的基因，以产生一个“永生化”的细胞系正常表型。在确认声带成纤维细胞转染后，用各种浓度的外源性TGF-β 1处理这些细胞（称为HVOX），并测定胶原分泌、迁移和增殖。此外，TGF-β信号通路的组成部分进行了检查，在此细胞line.Results：TGF-β刺激胶原蛋白的分泌和迁移，而不改变增殖的HVOX。HVOX组成型表达I型和II型TGF-β受体，以及Smad信号蛋白和所有TGF-β同种型的信使RNA。外源性TGF-β 1诱导Smad 2和Smad 3基因表达的时间依赖性改变。TGF-β在4和24小时均增加Smad 7表达。长期暴露于TGF-β 1降低TGF-β 1基因expression.Conclusions：洞察声带纤维化的潜在病理生理学可能会产生改善的治疗策略，以减轻声带瘢痕。我们的数据表明，TGF-β信号可能是旁分泌和自分泌在这个声带成纤维细胞系，因此，我们建议，TGF-β可能是一个合理的治疗目标，以预防和/或治疗声带纤维化，其假定的作用，在急性和慢性声带损伤，以及其对声带成纤维细胞的影响。
Objectives: We studied the effect of transforming growth factor (TGF)-beta on immortalized human vocal fold fibroblasts.Methods: Normal human vocal fold fibroblasts were subjected to sequential lentiviral transduction with genes for human telomerase (hTERT) and SV40 large T antigen in order to produce an "immortalized" cell line of normal phenotype. After confirmation of vocal fold fibroblast transfection, these cells, referred to as HVOX, were treated with various concentrations of exogenous TGF-beta 1 and assayed for collagen secretion, migration, and proliferation. In addition, components of the TGF-beta signaling pathway were examined in this cell line.Results: TGF-beta stimulated collagen secretion and migration without altering proliferation of HVOX. HVOX constitutive ly expressed type I and II TGF-beta receptors, as well as messenger RNA for the Smad signaling proteins and for all TGF-beta isoforms. Exogenous TGF-beta 1 induced temporally dependent alterations in Smad2 and Smad3 gene expression. TGF-beta increased Smad7 expression at both 4 and 24 hours. Prolonged exposure to TGF-P decreased TGF-beta 1 gene expression.Conclusions: Insight into the underlying pathophysiology of vocal fold fibrosis is likely to yield improved therapeutic strategies to mitigate vocal fold scarring. Our data suggest that TGF-beta signaling may be both paracrine and autocrine in this vocal fold fibroblast cell line, and we therefore propose that TGF-beta may be a reasonable target for therapies to prevent and/or treat vocal fold fibrosis, given its putative role in both acute and chronic vocal fold injury, as well as its effects on vocal fold fibroblasts.