Given that over 2% of the human genome codes for proteolytic enzymes and their inhibitors, it is not surprising that proteinases serve many physiologic-pathophysiological roles. In this context, we provide an overview of proteolytic mechanisms regulating inflammation, with a focus on cell signaling stimulated by the generation of inflammatory peptides; activation of the proteinase-activated receptor (PAR) family of G protein-coupled receptors (GPCR), with a mechanism in common with adhesion-triggered GPCRs (ADGRs); and by proteolytic ion channel regulation. These mechanisms are considered in the much wider context that proteolytic mechanisms serve, including the processing of growth factors and their receptors, the regulation of matrix-integrin signaling, and the generation and release of membrane-tethered receptor ligands. These signaling mechanisms are relevant for inflammatory, neurodegenerative, and cardiovascular diseases as well as for cancer. We propose that the inflammation-triggering proteinases and their proteolytically generated substrates represent attractive therapeutic targets and we discuss appropriate targeting strategies.

中文翻译：

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蛋白酶，它们的细胞外靶标和炎症信号。

鉴于超过2％的人类基因组编码蛋白水解酶及其抑制剂，因此蛋白酶发挥许多生理病理生理作用就不足为奇了。在这种情况下，我们提供了调节炎症的蛋白水解机制的概述，重点是由炎症肽的产生刺激的细胞信号传导。激活G蛋白偶联受体（GPCR）的蛋白酶激活受体（PAR）家族，其机制与粘附触发GPCR（ADGR）相同；并通过蛋白水解离子通道调节。在更广泛的蛋白水解机制起作用的范围内考虑了这些机制，包括生长因子及其受体的加工，基质整合素信号传导的调控以及膜束缚受体配体的产生和释放。这些信号传导机制与炎症，神经退行性疾病和心血管疾病以及癌症有关。我们建议触发炎症的蛋白酶及其蛋白水解产生的底物代表有吸引力的治疗目标，我们讨论适当的靶向策略。