1. KC21 Peptide Inhibits Angiogenesis and Attenuates Hypoxia-Induced Retinopathy
- Author
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Hung-I Yeh, Yih-Jer Wu, Chin-Ling Hsieh, Bo-Jeng Wang, Chun-Wei Chen, Ting Yi Tien, Chi-Sheng Lu, Yi-Nan Lee, Shin-Wei Wang, Cheng-Huang Su, and Min-Che Chen
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,Angiogenesis ,Pharmaceutical Science ,Neovascularization, Physiologic ,Peptide ,Angiogenesis Inhibitors ,030204 cardiovascular system & hematology ,Retinal Neovascularization ,Desmoglein ,p38 Mitogen-Activated Protein Kinases ,Neovascularization ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Therapeutic peptide ,Genetics ,medicine ,Animals ,Humans ,Hypoxia ,Protein kinase B ,Genetics (clinical) ,Cells, Cultured ,Cell Proliferation ,Endothelial Progenitor Cells ,chemistry.chemical_classification ,Matrigel ,Desmoglein 2 ,Cadherin ,Chemistry ,Endothelial colony-forming cells ,Peptide Fragments ,Cell biology ,Bevacizumab ,Mice, Inbred C57BL ,Disease Models, Animal ,Desmoglein-2 ,030104 developmental biology ,Matrix Metalloproteinase 9 ,Molecular Medicine ,Original Article ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Signal Transduction - Abstract
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. Electronic supplementary material The online version of this article (10.1007/s12265-019-09865-6) contains supplementary material, which is available to authorized users.
- Published
- 2018