Gene expression changes in therapeutic ultrasound-treated venous leg ulcers.
Gene expression changes in therapeutic ultrasound-treated venous leg ulcers.
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DOI：
10.3389/fmed.2023.1144182
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发表时间：
2023
影响因子：
3.9
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中科院分区：
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低频率、低强度的超声波以前曾被证明可以促进人类慢性伤口的愈合，但这些影响背后的机制尚不清楚。本研究的目的是评估低频(20 KHz)、低强度(100 mW/cm2)超声治疗的患者与假治疗患者清创的人静脉溃疡组织中基因表达的差异，以更好地了解潜在的生物学机制。32名受试者在假治疗或低频、低强度超声治疗一周后采集了清创的静脉性溃疡组织。在这些样本中，有7个样本(3个超声处理和4个假处理)获得了足够高质量的总RNA，可以用超高多重聚合酶链式反应(AmpliSeq)进行分析，并分析了超过24,000个基因的表达。以p <； 为0.0 5，倍数变化为2，超声组与假手术组差异显著，差异表达最多的基因包括与细胞代谢、增殖和免疫细胞信号调节有关的基因。基因集浓缩分析从上调基因中鉴定出20个显着富集基因集，从下调基因中鉴定出4个显着富集基因集。大多数来自上调基因的丰富基因集与细胞-细胞信号通路有关。从下调的基因中，最显著丰富的基因集是炎症反应基因集。这些发现表明，治疗性超声波最早在应用后一周就会影响慢性创面的细胞行为。考虑到慢性炎症在损害慢性创面愈合中所起的众所周知的作用，这些结果提示炎症基因的下调是超声介导静脉慢性创面愈合的可能的生物学机制。这种认识的增加最终可能导致超声设备的增强，以加速慢性伤口的愈合，提高患者的生活质量。
Low-frequency, low-intensity ultrasound has been previously shown to promote healing of chronic wounds in humans, but mechanisms behind these effects are poorly understood. The purpose of this study was to evaluate gene expression differences in debrided human venous ulcer tissue from patients treated with low-frequency (20 kHz), low-intensity (100 mW/cm2) ultrasound compared to a sham treatment in an effort to better understand the potential biological mechanisms. Debrided venous ulcer tissue was collected from 32 subjects one week after sham treatment or low-frequency, low-intensity ultrasound treatment. Of these samples, 7 samples (3 ultrasound treated and 4 sham treated) yielded sufficient quality total RNA for analysis by ultra-high multiplexed PCR (Ampliseq) and expression of more than 24,000 genes was analyzed. 477 genes were found to be significantly differentially expressed between the ultrasound and sham groups using cut-off values of p < 0.05 and fold change of 2. The top differentially expressed genes included those involved in regulation of cell metabolism, proliferation, and immune cell signaling. Gene set enrichment analysis identified 20 significantly enriched gene sets from upregulated genes and 4 significantly enriched gene sets from downregulated genes. Most of the enriched gene sets from upregulated genes were related to cell-cell signaling pathways. The most significantly enriched gene set from downregulated genes was the inflammatory response gene set. These findings show that therapeutic ultrasound influences cellular behavior in chronic wounds as early as 1 week after application. Considering the well-known role of chronic inflammation in impairing wound healing in chronic wounds, these results suggest that a downregulation of inflammatory genes is a possible biological mechanism of ultrasound-mediated venous chronic wound healing. Such increased understanding may ultimately lead to the enhancement of ultrasound devices to accelerate chronic wound healing and increase patient quality of life.