Tissue plasminogen activator and chronic kidney disease: More than a simple protease

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations

Abstract

Tissue plasminogen activator (tPA) is a member of the serine protease family that plays a pivotal role in the homeostasis of blood coagulation/fibrinolysis and matrix regulation. It is the FDA-approved first choice for embolic diseases such as ischemic stroke and acute myocardial infarction. However, its clinical usage has been significantly damped by its nonprotease-related side effects and toxicity. Recent studies discovered that tPA is a hybrid molecule with dual functions: protease and cytokine. As a protease, tPA converts plasminogen into active plasmin and participates in the fibrinolysis and matrix degradation. As a cytokine, tPA activates numerous receptor-mediated cellular signal transduction events contributing to its undesirable side effects and toxicity. tPA, as a cytokine, plays a detrimental role in the pathogenesis of chronic kidney disease (CKD) through multiple molecular mechanisms: 1) induces matrix metalloproteinases production through MAPK pathway triggering the epithelial mesenchymal transition; 2) promotes the survival, proliferation, and interstitial accumulation of fibroblasts in the diseased kidneys through p90RSK signaling; 3) promotes myofibroblast activation and macrophage migration by activating integrin signals; 4) modulates inflammation via NF-?B activation. This chapter will discuss the role of tPA and its receptormediated signaling cascades in the pathogenesis and progression of CKD.

Original languageEnglish (US)
Title of host publicationPlasminogen Activator
Subtitle of host publicationGenetic Factors, Functions and Clinical Applications
PublisherNova Science Publishers, Inc.
Pages53-68
Number of pages16
ISBN (Electronic)9781631173547
ISBN (Print)9781631173530
StatePublished - Jan 1 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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