NR4A1 is an endogenous inhibitor of vocal fold fibrosis.
NR4A1 is an endogenous inhibitor of vocal fold fibrosis.
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NR4A1是声带纤维化的内源性抑制剂。
DOI：
10.1002/lary.26678
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发表时间：
2017-09
期刊：
影响因子：
--
通讯作者：
Branski RC
中科院分区：
文献类型：
--
作者：
Hiwatashi N;Bing R;Kraja I;Branski RC
NR 4A 1最近被鉴定为TGF-β诱导的纤维化的内源性抑制剂，并且该核受体在组织健康或对声带损伤的反应中的作用尚未阐明。鉴于声带纤维化的临床意义，我们研究了体内声带伤口愈合期间NR 4A 1的表达以及NR 4A 1对体外声带成纤维细胞（VFF）的调节作用，最终目标是为这一具有挑战性的患者群体开发靶向疗法。在体内和体外在体内，定量大鼠声带损伤后NR 4A 1 mRNA表达的时间模式。在体外，NR 4A 1对TGF-β1介导的纤维化相关基因转录以及肌成纤维细胞分化和胶原凝胶收缩的作用在我们的人VFF系中被定量。小干扰RNA被用来改变NR 4A 1的表达，以进一步阐明这个复杂的系统。Nr 4a 1 mRNA在伤后1d开始升高，7 d达高峰。NR 4A 1的敲低导致VFF中COL 1A 1和TGF-β1在TGF-β1刺激下上调（均p<0.001）。NR 4A 1敲除还导致α平滑肌肌动蛋白阳性细胞增加（p=0.013）和响应于TGF-β1的收缩（p=0.002）。NR 4A 1尚未在声带健康或疾病中描述。声带损伤后TGF-β的上调与NR 4A 1表达的增加同时发生。这些数据为声带纤维化中持续TGF-β信号传导的治疗策略的开发提供了基础。N/A
NR4A1 was recently identified as an endogenous inhibitor of TGF-β-induced fibrosis and the role of this nuclear receptor has not been elucidated in tissue health or the response to injury in the vocal folds. Given the clinical implications of vocal fold fibrosis, we investigated NR4A1 expression during vocal fold wound healing in vivo and the regulatory roles of NR4A1 on vocal fold fibroblasts (VFFs) in vitro with the ultimate goal of developing targeted therapies for this challenging patient population. In vivo and in vitro In vivo, the temporal pattern of NR4A1 mRNA expression was quantified following rat vocal fold injury. In vitro, the role of NR4A1 on TGF-β1-mediated transcription of genes underlying fibrosis as well as myofibroblast differentiation and collagen gel contraction was quantified in our human VFF line. Small interfering RNA was employed to alter NR4A1 expression to further elucidate this complex system. Nr4a1 mRNA increased 1 day after injury and peaked at 7 days. Knockdown of NR4A1 resulted in upregulation of COL1A1 and TGF-β1 with TGF-β1 stimulation (both p<0.001) in VFFs. NR4A1 knockdown also resulted in increased alpha smooth muscle actin positive cells (p=0.013) and contraction (p=0.002) in response to TGF-β1. NR4A1 has not been described in vocal fold health or disease. Upregulation of TGF-β following vocal fold injury was concurrent with increased NR4A1 expression. These data provide a foundation for the development of therapeutic strategies given persistent TGF-β signaling in vocal fold fibrosis. N/A
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DOI：
10.1002/lary.25673
发表时间：
2016-05
期刊：
The Laryngoscope
影响因子：
--
作者：
Branski RC;Bing R;Kraja I;Amin MR
通讯作者：
Amin MR
影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1016/j.jsbmb.2015.04.016
发表时间：
2016-03
期刊：
The Journal of steroid biochemistry and molecular biology
影响因子：
--
作者：
Safe S;Jin UH;Morpurgo B;Abudayyeh A;Singh M;Tjalkens RB
通讯作者：
Tjalkens RB
影响因子：
4.3
作者：
Chang Z;Kishimoto Y;Hasan A;Welham NV
通讯作者：
Welham NV
DOI：
10.3410/b2-78
发表时间：
2010-11-11
期刊：
F1000 biology reports
影响因子：
--
作者：
Hinz B;Gabbiani G
通讯作者：
Gabbiani G