Kolhe Ravindra, Ghilzai Umar, Mondal Ashis K, Pundkar Chetan, Ahluwalia Pankaj, Sahajpal Nikhil S, Chen Jie, Isales Carlos M, Fulcher Mark, Fulzele Sadanand
Department of Pathology, Augusta University, Augusta, GA 30912, USA.
Department of Orthopedics, Augusta University, Augusta, GA 30912, USA.
Healthcare (Basel). 2021 Nov 20;9(11):1592. doi: 10.3390/healthcare9111592.
Trigger finger is a common yet vastly understudied fibroproliferative hand pathology, severely affecting patients' quality of life. Consistent trauma due to inadequate positioning within the afflicted finger's tendon/pulley system leads to cellular dysregulation and eventual fibrosis. While the genetic characteristics of the fibrotic tissue in the trigger finger have been studied, the pathways that govern the initiation and propagation of fibrosis are still unknown. The complete gene expression profile of the trigger finger has never been explored. Our study has used the Nanostring nCounter gene expression assay to investigate the molecular signaling involved in trigger finger pathogenesis. We collected samples from patients undergoing trigger finger ( = 4) release surgery and compared the gene expression to carpal tunnel tissue ( = 4). Nanostring nCounter analysis identified 165 genes that were differentially regulated; 145 of these genes were upregulated, whereas 20 genes were downregulated. We found that several collagen genes were significantly upregulated, and a regulatory matrix metalloproteinase (MMP), MMP-3, was downregulated. Bioinformatic analysis revealed that several known signaling pathways were dysregulated, such as the TGF-β1 and Wnt signaling pathways. We also found several novel signaling pathways (e.g., PI3K, MAPK, JAK-STAT, and Notch) differentially regulated in trigger finger. The outcome of our study helps in understanding the molecular signaling pathway involved in the pathogenesis of the trigger finger.
扳机指是一种常见但研究严重不足的纤维增生性手部疾病,严重影响患者的生活质量。由于患病手指的肌腱/滑车系统内位置不当导致的持续创伤会导致细胞失调并最终形成纤维化。虽然已经对扳机指中纤维化组织的遗传特征进行了研究,但控制纤维化起始和传播的途径仍然未知。扳机指的完整基因表达谱从未被探索过。我们的研究使用了Nanostring nCounter基因表达分析来研究扳机指发病机制中涉及的分子信号传导。我们从接受扳机指松解手术的患者(n = 4)中收集样本,并将基因表达与腕管组织(n = 4)进行比较。Nanostring nCounter分析确定了165个差异调节的基因;其中145个基因上调,而20个基因下调。我们发现几个胶原蛋白基因显著上调,而一种调节性基质金属蛋白酶(MMP),即MMP-3,下调。生物信息学分析表明,一些已知的信号通路失调,如TGF-β1和Wnt信号通路。我们还发现几个新的信号通路(如PI3K、MAPK、JAK-STAT和Notch)在扳机指中差异调节。我们的研究结果有助于了解扳机指发病机制中涉及的分子信号通路。