Linda Montavoci , Dario Romano , Leonardo Colombo , Aida Zulueta , Michele Dei Cas , Mariangela Scavone , Delfina Tosi , Clara Bernardelli , Alessandro Autelitano , Marco Trinchera , Luca Rossetti , Anna Caretti
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引用次数: 0
摘要
丝裂霉素 C 和其他抗增殖药物是广泛用于防止青光眼手术失败的非标示药物,失败的原因是特农氏成纤维细胞被激活以及随之而来的结膜下瘢痕过多。这些治疗方法虽然有效,但会带来一些严重的长期并发症,因此研究细胞毒性较低的化合物作为青光眼手术的辅助治疗至关重要。本研究旨在评估天然鞘脂合成抑制剂 Myriocin 对 TGF-β1 诱导的人真皮成纤维细胞肌成纤维细胞转化的影响和潜在细胞毒性。我们发现,myriocin 能显著降低参与纤维化过程的 αSMA、CTGF 和 MMP9 的转录水平。丝裂霉素 C 对这些促纤维化标志物的影响较小,而对成纤维细胞运动性的降低作用却不亚于肌球蛋白。在剂量相近的情况下,与长时间使用肌霉素相比,5 分钟的丝裂霉素 C 处理会持续影响人体真皮成纤维细胞的活力和增殖,这加强了已发表的关于这种天然化合物良好耐受性的数据。我们的研究结果使人们注意到,由于能有效减少成纤维细胞向肌成纤维细胞的转化,而且细胞毒性低,因此在青光眼手术中可以使用肌红蛋白作为辅助药物。
Use of Myriocin as co-adjuvant in glaucoma surgery: An in vitro study
Mitomycin C as well as other antiproliferative drugs are off-label agents widely used to prevent the failure of glaucoma surgery due to activation of Tenon’s fibroblasts and the ensuing excessive subconjunctival scarring. Though efficacious, these treatments are associated with some severe long-term complications, so it is crucial to investigate less cytotoxic compounds as adjuvant therapy in glaucoma surgery. The aim of this study was to evaluate the effect and potential cytotoxicity of Myriocin, a natural sphingolipid synthesis inhibitor, on TGF-β1-induced myofibroblasts transformation of human dermal fibroblasts. We found that myriocin significantly attenuated the transcript levels of αSMA, CTGF, and MMP9 which are involved in the fibrosis process. Mitomycin C poorly affects the same pro-fibrotic markers while reducing fibroblasts motility as much as myriocin. At similar doses, five minutes of mitomycin C treatment consistently affects human dermal fibroblast viability and proliferation compared to prolonged myriocin application, strengthening already published data on the good tolerability of this natural compound. Our results draw attention to the use of myriocin as an adjuvant in glaucoma surgery due to the effectiveness in reducing fibroblasts to myofibroblasts transformation and the low cytotoxicity.
期刊介绍:
IJBCB publishes original research articles, invited reviews and in-focus articles in all areas of cell and molecular biology and biomedical research.
Topics of interest include, but are not limited to:
-Mechanistic studies of cells, cell organelles, sub-cellular molecular pathways and metabolism
-Novel insights into disease pathogenesis
-Nanotechnology with implication to biological and medical processes
-Genomics and bioinformatics