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Plasminogen is a master regulator and a potential drug candidate for the healing of radiation wounds.
Cell Death & Disease ( IF 8.1 ) Pub Date : 2020-03-23 , DOI: 10.1038/s41419-020-2397-0 Mahsa Fallah 1 , Emil Viklund 1 , Assar Bäckman 2 , Jessica Brodén 2 , Bertil Lundskog 3 , Michael Johansson 4 , Michael Blomquist 4 , Malgorzata Wilczynska 1, 2 , Tor Ny 1
Cell Death & Disease ( IF 8.1 ) Pub Date : 2020-03-23 , DOI: 10.1038/s41419-020-2397-0 Mahsa Fallah 1 , Emil Viklund 1 , Assar Bäckman 2 , Jessica Brodén 2 , Bertil Lundskog 3 , Michael Johansson 4 , Michael Blomquist 4 , Malgorzata Wilczynska 1, 2 , Tor Ny 1
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Around 95% of cancer patients undergoing radiotherapy experience cutaneous side effects, and some develop radiation wounds or fibrosis. Currently, there is no effective treatment for these indications. We show here that plasminogen administration enhanced the healing of radiation wounds via pleiotropic effects on gene expression. Using RNA sequencing, we found that plasminogen downregulated the expression of genes in the TLR, TNF, WNT, MAPK, and TGF-β signaling pathways, and enhanced the anti-inflammatory effect of arachidonic acid, leading to significantly decreased inflammation and improved remodeling of granulation tissue compared with placebo treatment. In addition, plasminogen induced metabolic changes, including decreased glycolysis. Importantly, many of the factors downregulated by plasminogen are pro-fibrotic. Therefore, in radiation wounds with excessive inflammation, plasminogen is able to enhance and redirect the healing process, such that it more closely resembles physiological healing with significantly reduced risk for developing fibrosis. This makes plasminogen an attractive drug candidate for the treatment of radiation wounds in cancer patients.
中文翻译：
纤溶酶原是一种主要调节剂，也是治疗放射伤口的潜在候选药物。
大约 95% 接受放射治疗的癌症患者会出现皮肤副作用，有些会出现放射伤口或纤维化。目前，这些适应症尚无有效的治疗方法。我们在此表明，纤溶酶原的施用通过对基因表达的多效性作用增强了放射伤口的愈合。通过RNA测序，我们发现纤溶酶原下调TLR、TNF、WNT、MAPK和TGF-β信号通路中基因的表达，并增强花生四烯酸的抗炎作用，从而显着减少炎症并改善细胞重塑与安慰剂治疗相比，肉芽组织。此外，纤溶酶原诱导代谢变化，包括糖酵解减少。重要的是，许多被纤溶酶原下调的因素都是促纤维化的。因此，在炎症过度的放射伤口中，纤溶酶原能够增强和改变愈合过程，使其更接近于生理愈合，并显着降低发生纤维化的风险。这使得纤溶酶原成为治疗癌症患者放射伤口的有吸引力的候选药物。
更新日期：2020-03-24
中文翻译：
纤溶酶原是一种主要调节剂，也是治疗放射伤口的潜在候选药物。
大约 95% 接受放射治疗的癌症患者会出现皮肤副作用，有些会出现放射伤口或纤维化。目前，这些适应症尚无有效的治疗方法。我们在此表明，纤溶酶原的施用通过对基因表达的多效性作用增强了放射伤口的愈合。通过RNA测序，我们发现纤溶酶原下调TLR、TNF、WNT、MAPK和TGF-β信号通路中基因的表达，并增强花生四烯酸的抗炎作用，从而显着减少炎症并改善细胞重塑与安慰剂治疗相比，肉芽组织。此外，纤溶酶原诱导代谢变化，包括糖酵解减少。重要的是，许多被纤溶酶原下调的因素都是促纤维化的。因此，在炎症过度的放射伤口中，纤溶酶原能够增强和改变愈合过程，使其更接近于生理愈合，并显着降低发生纤维化的风险。这使得纤溶酶原成为治疗癌症患者放射伤口的有吸引力的候选药物。
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