KC21 Peptide Inhibits Angiogenesis and Attenuates Hypoxia-Induced Retinopathy

Autor: 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, Min-Che Chen
Rok vydání: 2018
Předmět:
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
Zdroj: Journal of Cardiovascular Translational Research
ISSN: 1937-5395
Popis: 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.
Databáze: OpenAIRE
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