Zaohe Sun,
Guangming Wan ,
Shenzhi Liang,
Cheng Qian
Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, PR China;
For correspondence:- Guangming Wan
Email: hnzz20080101@163.com
Accepted: 28 April 2019
Published: 31 May 2019
Citation:
Sun Z, Wan G, Liang S, Qian C.
Effect of bone morphogenetic protein-2 on diabetic retinopathy and its mechanism of action. Trop J Pharm Res 2019; 18(5):1069-1076
doi:
10.4314/tjpr.v18i5.22
© 2019 The authors.
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Abstract
Purpose: To investigate the effect of bone morphogenetic protein-2 (BMP-2) on human retinal vascular endothelial cells (RECs) and human retinal pigment epithelial cells (RPE) cultured in high glucose (HG) in vitro, and the underlying mechanism.
Methods: Cell counting kit-8 (CCK-8) was used to determine cell proliferation while Western blot was used to assay the expressions of extracellular matrix and angiogenesis-related factors, expressions of cytokines and chemokines were assessed by quantitative real time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Changes in Smad, ERK, JNK and p38MAPK signal pathway were measured by transfection and interference.
Results: The level of expression of BMP-2 in HG group was higher than that in normal glucose (NG) culture group. The expressions of angiogenesis-related factors i.e. vascular endothelial growth factor (VEGF) and intercellular cell adhesion molecule-1 (ICAM1), pro-inflammatory factors i.e. IL-6 and chemokine monocyte chemokine protein-1 (MCP1), increased significantly in HG group compared to NG and HG + BMP-2 groups. Phosphorylation of Smad1/5/8 and activation of ERK, JNK and p38MAPK signaling pathways were enhanced by BMP-2.
Conclusion: These results suggest that BMP-2 promotes angiogenesis and enhances the expressions of inflammatory cytokines via Smad signaling pathway.
Keywords: Diabetic retinopathy, Retina, Pigment epithelial cells, Vascular endothelial cells, Bone morphogenetic protein-2