Evaluation of the C-domain of heparanase during AGE-induced macrophage inflammtory response

Qin,Qiaojing; Xu,Guang; Qi,Weiwei; Guo,Mei; Wang,Zhaoxia; Xu,Wangjie; Qiao,Zhongdong; Gu,Yong; Niu,Jianying

doi:10.3892/etm.2017.4609

August-2017 Volume 14 Issue 2

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August-2017 Volume 14 Issue 2

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Evaluation of the C-domain of heparanase during AGE-induced macrophage inflammtory response

Authors:
- Qiaojing Qin
- Guang Xu
- Weiwei Qi
- Mei Guo
- Zhaoxia Wang
- Wangjie Xu
- Zhongdong Qiao
- Yong Gu
- Jianying Niu
View Affiliations / Copyright

Affiliations: Department of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, P.R. China, School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, P.R. China

Copyright: © Qin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 1017-1022
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Published online on: June 15, 2017

https://doi.org/10.3892/etm.2017.4609
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Abstract

Diabetic vasculopathy is intensified by macrophage inflammation caused by advanced glycation end products (AGEs). Heparanase (HPA) is a unique endoglycosidase, which cleaves heparan sulfate proteoglycans (HSPGs) including syndecan-1 (Syn-1) to further stimulate macrophage cell migration and inflammation. The present study was planned to evaluated the role of C-domain (if any) of HPA in AGE inflammatory response in macrophages. Cell viability was assessed using MTT assay, migration assay, ELISA for tumor necrosis factor‑α (TNF‑α), interleukin-1β (IL-1β) levels, mRNA expression by RT-PCR and heparan degrading enzyme assay for HPA activity. In the present study, we found that pretreatment with anti-HPA antibody, which recognizes the C-domain of HPA inhibited macrophage migration, secretion of IL-1β and TNF-α as well as decreased HPA enzymatic activity and increased Syn-1 protein expression in AGE-induced macrophages. Compared with anti-HPA antibody pretreatment, co-pretreatment with anti-HPA plus Syn-1 antibodies promoted macrophage migration, and secretion of IL-1β and TNF-α significantly in AGE-induced macrophages. In addition, pretreatment with anti-HPA or anti‑HPA plus Syn-1 antibodies did not markedly change the mRNA levels of IL-1β and TNF-α concentration AGE‑treated macrophages. The results showed that C-domain of HPA mediates AGE-induced macrophage migration and inflammatory cytokine release via Syn-1 protein expression. Furthermore, C-domain of HPA may have a key role in diabetic vascular complication‑associated inflammatory response.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Evaluation of the C-domain of heparanase during AGE-induced macrophage inflammtory response

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