title: Inorganic polyphosphate: a key modulator of inflammation.
abstract: 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 P2Y1receptors, 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.
authors.affiliation: Department of Medical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.|Microanatomy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.|Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, MO, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Hassanian
authors.affiliation: Molecular Medicine Group, Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.|Departments of Medical Oncology and Neurology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Avan
authors.affiliation: Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, MO, USA.|Department of Tissue Engineering and Regenerative Medicine, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Ardeshirylajimi
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D002318:Cardiovascular Diseases / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000378:metabolism; D000076225:Mechanistic Target of Rapamycin Complex 2 / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D011122:Polyphosphates / Q000737:chemistry*; D015398:Signal Transduction
chemical_list: D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D006657:Histones; D018836:Inflammation Mediators; D016328:NF-kappa B; D011122:Polyphosphates; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2
keywords: blood coagulation; inflammation; platelets; polyphosphates; thrombosis