关键词: DNA aptamer fibrinolysis hepatocyte growth factor mesothelial mesenchymal transition peritoneal adhesion

Mesh : Aptamers, Nucleotide / chemistry pharmacology Hepatocyte Growth Factor / metabolism Tissue Adhesions / prevention & control Humans Fibrinolysis / drug effects Epithelial-Mesenchymal Transition / drug effects Biocompatible Materials / chemistry pharmacology Materials Testing Particle Size Postoperative Complications / prevention & control

来  源:   DOI:10.1021/acsabm.4c00507

Abstract:
Postoperative peritoneal adhesion (PPA) is a prevalent complication of abdominal surgery, posing a significant hindrance to postsurgical recovery. Although several strategies have been developed to alleviate and prevent adhesions, their efficacy remains unsatisfactory. For the first time, we studied the therapeutic effect and mechanism of our recently developed thermally stable oligonucleotide-based mimetics of hepatocyte growth factor (HGF DNA aptamer) to prevent PPA. The HGF DNA aptamer effectively inhibited canonical TGF-β1 signaling transduction, partially suppressing mesothelial mesenchymal transition. Additionally, the aptamer, respectively, upregulated and downregulated the expression of tissue plasminogen activator and plasminogen activator inhibitor 1, thereby enhancing fibrinolytic activity. As a pleiotropic factor, the HGF DNA aptamer also enhanced the migratory and proliferative capacities of mesothelial cells. Finally, the aptamer demonstrated a higher level of effectiveness in preventing PPAs than the commercially available antiperitoneal adhesion barrier, Seprafilm. Due to its therapeutic benefits, excellent stability, biosafety, cost-effectiveness, and versatility, the HGF DNA aptamer demonstrates promise for preventing PPA in future clinical settings.
摘要:
术后腹膜粘连(PPA)是腹部手术常见的并发症,对术后恢复构成重大障碍。尽管已经开发了几种策略来减轻和预防粘连,其疗效仍不能令人满意。第一次,我们研究了我们最近开发的肝细胞生长因子(HGFDNA适体)的热稳定寡核苷酸模拟物预防PPA的治疗效果和机制。HGFDNA适体有效抑制经典TGF-β1信号转导,部分抑制间皮间质转化。此外,适体,分别,上调和下调组织纤溶酶原激活物和纤溶酶原激活物抑制剂1的表达,从而增强纤溶活性。作为一个多效性因素,HGFDNA适体还增强了间皮细胞的迁移和增殖能力。最后,与市售的抗腹膜粘连屏障相比,适体在预防PPAs方面表现出更高的有效性,Seprafilm.由于其治疗益处,出色的稳定性,生物安全,成本效益,和多功能性,HGFDNA适体显示了在未来临床环境中预防PPA的前景。
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