• Shock · May 2022

    Platelets Derived Transthyretin Participate In The Development of Sepsis Associated Acute Kidney Injury by Inducing Oxidative Stress and Apoptosis of Renal Tubular Epithelial Cells.

    • Diyu Lv, Ying Zhang, Chunmei Wang, Yi Gu, Yang Zhang, and Xiuhua Li.
    • Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
    • Shock. 2022 May 1; 57 (5): 722-731.

    AbstractThe pathophysiology of sepsis-associated acute kidney injury (S-AKI) is not well elucidated. Platelets have been reported to play a critical role in the pathogenesis of AKI, but the true mechanism remains unknown. Herein, we established a mouse model of S-AKI by cecal ligation and puncture (CLP). Ticagrelor was given 24 h before and after CLP by gastric gavage. Platelets were isolated and analyzed by the label-free proteome approach to identify platelet-derived damage-associated molecular patterns (DAMPs). Our results demonstrated that, among all differentially expressed proteins (DEPs), platelet-derived transthyretin (TTR) exerted effects in S-AKI. To examine the direct effects of platelet TTR on human renal proximal tubule epithelial (HK2) cells damage, platelets were co-cultured with HK2 cells. The results indicated that platelet TTR can cause reactive oxygen species production and apoptosis in HK2 cells. Further research found that platelet TTR can also result in increased levels of mRNA and protein for protein kinase B (AKT), phosphatidylinositol 3-kinase (PI3K), and extracellular regulated protein kinase (ERK), as analyzed by real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. In conclusion, platelet-derived TTR may be one kind of DAMPs that plays an important role in the development of S-AKI.Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.

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