Inorganic polyphosphate: a key modulator of inflammation

Hassanian, S. M. and Avan, A. and Ardeshirylajimi, A. (2017) Inorganic polyphosphate: a key modulator of inflammation. Journal of Thrombosis and Haemostasis, 15 (2). pp. 213-218.

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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

Item Type: Article
Additional Information: Cited By :11 Export Date: 16 February 2020 CODEN: JTHOA Correspondence Address: Hassanian, S.M.; Department of Medical Biochemistry, School of Medicine, Mashhad University of Medical SciencesIran; email:
Uncontrolled Keywords: blood coagulation inflammation platelets polyphosphates thrombosis advanced glycation end product receptor bradykinin cell adhesion molecule high mobility group B1 protein histone immunoglobulin enhancer binding protein inorganic polyphosphate kallikrein kinin mammalian target of rapamycin nuclear protein polyphosphate purinergic P2Y1 receptor unclassified drug advanced glycation end product autacoid HMGB1 protein, human mammalian target of rapamycin complex 1 mammalian target of rapamycin complex 2 bacterium blood clotting blood vessel permeability cardiovascular disease complement system diabetes mellitus drug targeting eukaryote human inflammatory disease kallikrein kinin system malignant neoplasm metabolic disorder nonhuman regulatory mechanism Review sepsis signal transduction animal chemistry Escherichia coli metabolism mouse neoplasm Animals Cardiovascular Diseases Glycation End Products, Advanced Histones HMGB1 Protein Humans Inflammation Mediators Mechanistic Target of Rapamycin Complex 1 Mechanistic Target of Rapamycin Complex 2 Mice Neoplasms NF-kappa B
Subjects: QU Biochemistry
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib3 lib3
Date Deposited: 29 Apr 2020 05:13
Last Modified: 29 Apr 2020 05:13

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