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Effect of bone morphogenetic protein-2 on diabetic retinopathy and its mechanism of action
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 (qRTPCR) 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.
