Inorganic Polyphosphate: A Key Modulator of Inflammation Publisher Pubmed



Hassanian SM^{1, 2, 3} ; Avan A^{4, 5} ; Ardeshirylajimi A^{3, 6} Show Affiliations
Source: Journal of Thrombosis and Haemostasis Published:2017

Abstract

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 P2Y1 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. © 2016 International Society on Thrombosis and Haemostasis