KC21 Peptide Inhibits Angiogenesis and Attenuates Hypoxia-Induced Retinopathy

Desmogleins (Dsg2) are the major components of desmosomes. Dsg2 has five extracellular tandem cadherin domains (EC1-EC5) for cell-cell interaction. We had previously confirmed the Dsg2 antibody and its epitope (named KC21) derived from EC2 domain suppressing epithelial-mesenchymal transition and inv...

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Published in:Journal of cardiovascular translational research 2019-08, Vol.12 (4), p.366-377
Main Authors: Lu, Chi-Sheng, Lee, Yi-Nan, Wang, Shin-Wei, Wu, Yih-Jer, Su, Cheng-Huang, Hsieh, Chin-Ling, Tien, Ting Yi, Wang, Bo-Jeng, Chen, Min-Che, Chen, Chun-Wei, Yeh, Hung-I
Format: Article
Language:English
Subjects:
Biomedical Engineering and Bioengineering
Biomedicine
Cardiology
Human Genetics
Medicine
Medicine & Public Health
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Summary:Desmogleins (Dsg2) are the major components of desmosomes. Dsg2 has five extracellular tandem cadherin domains (EC1-EC5) for cell-cell interaction. We had previously confirmed the Dsg2 antibody and its epitope (named KC21) derived from EC2 domain suppressing epithelial-mesenchymal transition and invasion in human cancer cell lines. Here, we screened six peptide fragments derived from EC2 domain and found that KR20, the parental peptide of KC21, was the most potent one on suppressing endothelial colony-forming cell (ECFC) tube-like structure formation. KC21 peptide also attenuated migration but did not disrupt viability and proliferation of ECFCs, consistent with the function to inhibit VEGF-mediated activation of p38 MAPK but not AKT and ERK. Animal studies showed that KC21 peptides suppressed capillary growth in Matrigel implant assay and inhibited oxygen-induced retinal neovascularization. The effects were comparable to bevacizumab (Bev). In conclusion, KC21 peptide is an angiogenic inhibitor potentially useful for treating angiogenesis-related diseases.
ISSN:1937-5387
1937-5395
DOI:10.1007/s12265-019-09865-6