Histidine-rich glycoprotein (HRGP): Pleiotropic and paradoxical effects on macrophage, tumor microenvironment, angiogenesis, and other physiological and pathological processes

Yixiao Pan; Lu Deng; Hai Wang; Kang He; Qiang Xia

doi:10.1016/j.gendis.2020.07.015

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Histidine-rich glycoprotein (HRGP): Pleiotropic and paradoxical effects on macrophage, tumor microenvironment, angiogenesis, and other physiological and pathological processes

更新时间：2022-06-24

- Histidine-rich glycoprotein (HRGP): Pleiotropic and paradoxical effects on macrophage, tumor microenvironment, angiogenesis, and other physiological and pathological processes
- Genes & Diseases Vol. 9, Issue 2, (2022)
- 作者机构：
  
  Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University,Shanghai,PR China,200120
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2020.07.015
  CLC：
- Published：2022，
  
  Published Online：1 March 2022，
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Yixiao Pan, Lu Deng, Hai Wang, et al. Histidine-rich glycoprotein (HRGP): Pleiotropic and paradoxical effects on macrophage, tumor microenvironment, angiogenesis, and other physiological and pathological processes. [J]. Genes & Diseases 9(2).(2022)
DOI：

Yixiao Pan, Lu Deng, Hai Wang, et al. Histidine-rich glycoprotein (HRGP): Pleiotropic and paradoxical effects on macrophage, tumor microenvironment, angiogenesis, and other physiological and pathological processes. [J]. Genes & Diseases 9(2).(2022) DOI： 10.1016/j.gendis.2020.07.015.

摘要

Abstract

Histidine-rich glycoprotein (HRGP) is a relatively less known glycoprotein

but it is abundant in plasma with a multidomain structure

which allows it to interact with many ligands and regulate various biological processes. HRGP ligands includes heme

thrombospondin

plasmin/plasminogen

heparin/heparan sulfate

fibrinogen

tropomyosin

IgG

FcγR

C1q. In many conditions

the histidine-rich region of HRGP strengthens ligand binding following interaction with Zn

or exposure to low pH

such as sites of tissue injury or tumor growth. The multidomain structure and diverse ligand binding attributes of HRGP indicates that it can act as an extracellular adaptor protein

connecting with different ligands

especially on cell surfaces. Also

HRGP can selectively target IgG

which blocks the production of soluble immune complexes. The most common cell surface ligand of HRGP is heparan sulfate proteoglycan

and the interaction is also potentiated by elevated Zn

concentration and low pH. Recent reports have shown that HRGP can modulate macrophage polarization and possibly regulate other physiological processes such as angiogenesis

anti-tumor immune response

fibrinolysis and coagulation

soluble immune complex clearance and phagocytosis of apoptotic/necrosis cells. In addition

it has also been reported that HRGP has antibacterial and anti-HIV infection effects and may be used as a novel clinical biomarker accordingly. This review outlines the molecular

structural and biological properties of HRGP as well as presenting an update on the function of HRGP in various physiological processes.

关键词

Keywords

AngiogenesisHistidine-rich glycoproteinMacrophage polarizationThrombospondinTumor

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