Inhibition of Angiogenesis by the First Type I Repeat Peptides of Thrombospondin-1.
10.11637/kjpa.2015.28.4.223
- Author:
Bo Im YOO
1
;
Goo Bo JEONG
Author Information
1. Department Anatomy and Cell Biology, Graduate School of Medicine, Gachon University, Incheon, Korea. gbjeong@gachon.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Angiogenesis;
Thrombospondin-1;
TSR-1;
Bovine TSP-1;
Endothelial cell
- MeSH:
Amino Acid Sequence;
Animals;
Apoptosis;
Biological Phenomena;
Endothelial Cells;
Extracellular Matrix;
Flow Cytometry;
Humans;
Inflammation;
Mice;
Microvessels;
Peptides*;
Thrombospondin 1;
Vertebrates;
Wound Healing
- From:Korean Journal of Physical Anthropology
2015;28(4):223-238
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Angiogenesis is the fundamental biological phenomenon in the development of vertebrates and various pathophysiological process such as cancer, inflammation and wound healing. Thrombospondin-1 is a well-known anti-angiogenic molecule which is distributed in the extracellular matrix of various tissues. The second and third type I repeats of human TSP-1 have inhibitory effects on endothelial cell migration and induce angiogenesis inhibition. However the role of the first type I repeat was not elucidated. In addition, the first type I repeat of bovine TSP-1 has CSVTCG amino acid sequence which is known to have anti-angiogenic activity. In the present study, we compared the inhibition of angiogenesis to investigate the role of the first type I repeat of the human and bovine TSP-1. Matrigel was mixed with or without TSR-1 peptides and then injected into C57BL/6J mice. We compared angiogenesis inhibition activity by hemoglobin assay, microvessel density and optical density value after 7 days. Furthermore, inhibition of angiogenesis was confirmed on CAM assay by TSR-1 peptides. For in vitro angiogenesis assay, TSR-1 peptides were treated on the proliferation, migration, and tube formation assay of HUVEC. Apoptosis effect of TSR-1 peptides was confirmed by apoptosis assay kit and flow cytometry. Bovine and human TSR-1 peptides blocked neovascularization in in vivo Matrigel plug assay and CAM assay at 10 microM. Bovine TSR-1 peptides have shown stronger angiogenesis inhibition in bFGF-induced angiogenesis than human TSR-1 and CSVTCG peptides. However, all of TSR-1 peptides inhibit migration and tube formation of HUVEC in in vitro. Furthermore, these peptides also induced apoptosis of HUVEC. These results suggest that TSR-1 peptides of bovine and human TSP-1 have angiogenesis inhibition activity.