Programa de Pós-graduação em Genética e Bioquímica, Instituto de Biotecnologia, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil; Departamento de Ciências Fisiológicas, Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil.
Departamento de Genética e Evolução, Universidade Federal de São Carlos, São Paulo, Brazil.
Int Immunopharmacol. 2021 Jul;96:107801. doi: 10.1016/j.intimp.2021.107801. Epub 2021 May 24.
Cystatins are natural inhibitors of cysteine peptidases that are found practically in all living organisms. CaneCPI-5 is a sugarcane cystatin with inhibitory activity against human cathepsins B, K and L, which are cysteine proteases highly expressed in a variety of pathological conditions, usually marked by persistent inflammation and processing of the extracellular matrix. This work evaluated the effects of daily administration of the recombinant cystatin CaneCPI-5 [0.01, 0.1 or 1.0 μg in 10 μL of Phosphate-Buffered Saline (PBS)] on the inflammatory, angiogenic and fibrogenic components during chronic inflammatory response induced by subcutaneous sponge implants. The anti-inflammatory effect of treatment with CaneCPI-5 was confirmed by reduction of the levels of the pro-inflammatory mediators TNF-α, CXCL1 and CCL2/JE/MCP-1, as well as the activity of the myeloperoxidase and n-acetyl-β-D-glucosaminidase. Treatment with CaneCPI-5 promoted angiogenesis in the implants, increasing the production of cytokines VEGF and FGF and the formation of new blood vessels. Finally, the administration of the recombinant cystatin favored the production of the pro-fibrogenic cytokine TGF-β1 and collagen deposition next to the implants. Together, these results show the potential therapeutic application of CaneCPI-5 as an anti-inflammatory agent, capable of favoring angiogenesis and fibrogenesis processes, necessary for tissue repair.
组织蛋白酶抑制剂是存在于几乎所有生物体中的半胱氨酸蛋白酶抑制剂。甘蔗 CPI-5 是一种甘蔗半胱氨酸蛋白酶抑制剂，对人组织蛋白酶 B、K 和 L 具有抑制活性，这些酶是在多种病理条件下高度表达的半胱氨酸蛋白酶，通常以持续的炎症和细胞外基质的处理为特征。本研究评估了重组半胱氨酸蛋白酶抑制剂 CaneCPI-5（0.01、0.1 或 1.0μg 在 10μL 磷酸盐缓冲液（PBS）中）对皮下海绵植入物诱导的慢性炎症反应中炎症、血管生成和纤维生成成分的影响。CaneCPI-5 治疗的抗炎作用通过降低促炎介质 TNF-α、CXCL1 和 CCL2/JE/MCP-1 的水平以及髓过氧化物酶和 N-乙酰-β-D-氨基葡萄糖苷酶的活性得到证实。CaneCPI-5 处理促进了植入物中的血管生成，增加了细胞因子 VEGF 和 FGF 的产生和新血管的形成。最后，重组半胱氨酸蛋白酶的给药有利于植入物附近促纤维化细胞因子 TGF-β1 和胶原蛋白的沉积。总之，这些结果表明 CaneCPI-5 作为一种抗炎剂具有潜在的治疗应用，能够促进血管生成和纤维化过程，这是组织修复所必需的。
