Institute of Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University, Magdeburg, Germany.
Department of Biotechnology, University of Sargodha, Sargodha, Pakistan.
Curr Opin Hematol. 2019 Jan;26(1):41-50. doi: 10.1097/MOH.0000000000000473.
The serine protease activated protein C (aPC) was initially characterized as an endogenous anticoagulant, but in addition conveys anti-inflammatory, barrier-protective, and pro cell-survival functions. Its endogenous anticoagulant function hampered the successful and continuous implantation of aPC as a therapeutic agent in septic patients. However, it became increasingly apparent that aPC controls cellular function largely independent of its anticoagulant effects through cell-specific and context-specific receptor complexes and intracellular signaling pathways. The purpose of this review is to outline the mechanisms of aPC-dependent cell signaling and its intracellular molecular targets.
With the advent of new therapeutic agents either modulating directly and specifically the activity of coagulation proteases or interfering with protease-activated receptor signaling a better understanding not only of the receptor mechanisms but also of the intracellular signaling mechanisms controlled by aPC in a disease-specific and context-specific fashion, is required to tailor new therapeutic approaches based on aPC's anti-inflammatory, barrier-protective, and pro cell-survival functions.
This review summarizes recent insights into the intracellular signaling pathways controlled by aPC in a cell-specific and context-specific fashion. We focus on aPC-mediated barrier protection, inhibition of inflammation, and cytoprotecting within this review.
丝氨酸蛋白酶激活蛋白 C（aPC）最初被描述为一种内源性抗凝剂，但它还具有抗炎、保护屏障和促进细胞存活的功能。其内源性抗凝功能阻碍了 aPC 作为治疗败血症患者的药物的成功和持续应用。然而，越来越明显的是，aPC 通过细胞特异性和上下文特异性受体复合物以及细胞内信号通路来控制细胞功能，而这些功能在很大程度上独立于其抗凝作用。本文综述的目的是概述 aPC 依赖性细胞信号转导及其细胞内分子靶标。
随着新型治疗药物的出现，这些药物要么直接且特异性地调节凝血蛋白酶的活性，要么干扰蛋白酶激活受体信号转导，不仅需要更好地了解受体机制，还需要更好地了解 aPC 以疾病特异性和上下文特异性方式控制的细胞内信号转导机制，以便根据 aPC 的抗炎、保护屏障和促进细胞存活功能制定新的治疗方法。
本文综述了最近关于 aPC 以细胞特异性和上下文特异性方式控制的细胞内信号通路的见解。我们在此综述中重点关注 aPC 介导的屏障保护、炎症抑制和细胞保护作用。
