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Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2013

Open Access 01-12-2013 | Original investigation

Heparanase induced by advanced glycation end products (AGEs) promotes macrophage migration involving RAGE and PI3K/AKT pathway

Authors: Qiaojing Qin, Jianying Niu, Zhaoxia Wang, Wangjie Xu, Zhongdong Qiao, Yong Gu

Published in: Cardiovascular Diabetology | Issue 1/2013

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Abstract

Background

Advanced glycation end products (AGEs), inflammatory-associated macrophage migration and accumulation are crucial for initiation and progression of diabetic vascular complication. Enzymatic activity of heparanase (HPA) is implicated strongly in dissemination of metastatic tumor cells and cells of the immune system. In addition, HPA enhances the phosphorylation of selected signaling molecules including AKT pathway independent of enzymatic activity. However, virtually nothing is presently known the role of HPA during macrophage migration exposed to AGEs involving signal pathway.

Methods

These studies were carried out in Ana-1 macrophages. Macrophage viability was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays. HPA and AKT protein expression in macrophages are analysed by Western blotting and HPA mRNA expression by real time quantitative RT-PCR. Release of HPA was determined by ELISA. Macrophage migration was assessed by Transwell assays.

Results

HPA protein and mRNA were found to be increased significantly in AGEs-treated macrophages. Pretreatment with anti-HPA antibody which recognizes the nonenzymatic terminal of HPA prevented AGEs-induced AKT phosphorylation and macrophage migration. LY294002 (PI3k/AKT inhibitor) inhibited AGEs-induced macrophage migration. Furthermore, pretreatment with anti-receptor for advanced glycation end products (RAGE) antibody attenuated AGEs-induced HPA expression, AKT phosphorylation and macrophage migration.

Conclusions

These data indicate that AGEs-induced macrophage migration is dependent on HPA involving RAGE-HPA-PI3K/AKT pathway. The nonenzymatic activity of HPA may play a key role in AGEs-induced macrophage migration associated with inflammation in diabetic vascular complication.
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Metadata
Title
Heparanase induced by advanced glycation end products (AGEs) promotes macrophage migration involving RAGE and PI3K/AKT pathway
Authors
Qiaojing Qin
Jianying Niu
Zhaoxia Wang
Wangjie Xu
Zhongdong Qiao
Yong Gu
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2013
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/1475-2840-12-37

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