1. An Ixodes persulcatus Inhibitor of Plasmin and Thrombin Hinders Keratinocyte Migration, Blood Coagulation, and Endothelial Permeability.
- Author
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Berger M, Rosa da Mata S, Pizzolatti NM, Parizi LF, Konnai S, da Silva Vaz I Jr, Seixas A, and Tirloni L
- Subjects
- Animals, Humans, Female, Endothelial Cells metabolism, Wound Healing, Ixodes metabolism, Fibrinolysin metabolism, Keratinocytes metabolism, Thrombin metabolism, Cell Movement, Blood Coagulation physiology
- Abstract
The skin is the first host tissue that the tick mouthparts, tick saliva, and a tick-borne pathogen contact during feeding. Tick salivary glands have evolved a complex and sophisticated pharmacological arsenal, consisting of bioactive molecules, to assist blood feeding and pathogen transmission. In this work, persulcatin, a multifunctional molecule that targets keratinocyte function and hemostasis, was identified from Ixodes persulcatus female ticks. The recombinant persulcatin was expressed and purified and is a 25-kDa acidic protein with 2 Kunitz-type domains. Persulcatin is a classical tight-binding competitive inhibitor of proteases, targeting plasmin (K
i : 28 nM) and thrombin (Ki : 115 nM). It blocks plasmin generation on keratinocytes and inhibits their migration and matrix protein degradation; downregulates matrix metalloproteinase 2 and matrix metalloproteinase 9; and causes a delay in blood coagulation, endothelial cell activation, and thrombin-induced fibrinocoagulation. It interacts with exosite I of thrombin and reduces thrombin-induced endothelial cell permeability by inhibiting vascular endothelial-cadherin disruption. The multifaceted roles of persulcatin as an inhibitor and modulator within the plasminogen-plasmin system and thrombin not only unveil further insights into the intricate mechanisms governing wound healing but also provide a fresh perspective on the intricate interactions between ticks and their host organisms., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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