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Inorganic polyphosphate: a key modulator of inflammation
Author(s) -
Hassanian S. M.,
Avan A.,
Ardeshirylajimi A.
Publication year - 2017
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.13580
Subject(s) - proinflammatory cytokine , inflammation , hmgb1 , microbiology and biotechnology , glycation , signal transduction , chemistry , cancer research , immunology , receptor , biology , biochemistry
Summary Inorganic polyphosphate (PolyP) is a molecule with prothrombotic and proinflammatory properties in blood. PolyP activates the NF‐κB signaling pathway, increases the expression of cell surface adhesion molecules and disrupts the vascular barrier integrity of endothelial cells. PolyP‐induced NF‐κB activation and vascular hyperpermeability are regulated by the mammalian target of rapamycin complex‐1 (mTORC1) and mTORC2 pathways, respectively. Through interaction with receptor for advanced glycation end products (RAGE) and P2Y 1 receptors, PolyP dramatically amplifies the proinflammatory responses of nuclear proteins. Moreover, PolyP‐mediated activation of the contact pathway results in activation of the kallikrein–kinin system, which either directly or in cross‐talk with the complement system induces inflammation in both cellular and animal systems. Thus, polyP is a novel therapeutic target for the treatment of metabolic and acute/chronic proinflammatory diseases, including severe sepsis, diabetes, cardiovascular disease and cancer. In this review, we discuss recent findings on the inflammatory properties of polyP and propose a model to explain the molecular mechanism of proinflammatory effects of this molecule in different systems.