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Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation
- Source :
- Journal of molecular medicine (Berlin, Germany). 95(3)
- Publication Year :
- 2016
-
Abstract
- BPC 157, a pentadecapeptide with extensive healing effects, has recently been suggested to contribute to angiogenesis. However, the underlying mechanism is not yet clear. The present study aimed to explore the potential therapeutic effect and pro-angiogenic mechanism of BPC 157. As demonstrated by the chick chorioallantoic membrane (CAM) assay and endothelial tube formation assay, BPC 157 could increase the vessel density both in vivo and in vitro, respectively. BPC 157 could also accelerate the recovery of blood flow in the ischemic muscle of the rat hind limb as detected by laser Doppler scanning, indicating the promotion of angiogenesis. Histological analysis of the hind limb muscle confirmed the increased number of vessels and the enhanced vascular expression of vascular endothelial growth factor receptor 2 (VEGFR2) in rat with BPC 157 treatment. In vitro study using human vascular endothelial cells further confirmed the increased mRNA and protein expressions of VEGFR2 but not VEGF-A by BPC 157. In addition, BPC 157 could promote VEGFR2 internalization in vascular endothelial cells which was blocked in the presence of dynasore, an inhibitor of endocytosis. BPC 157 time dependently activated the VEGFR2-Akt-eNOS signaling pathway which could also be suppressed by dynasore. The increase of endothelial tube formation induced by BPC 157 was also inhibited by dynasore. This study demonstrates the pro-angiogenic effects of BPC 157 that is associated with the increased expression, internalization of VEGFR2, and the activation of VEGFR2-Akt-eNOS signaling pathway. BPC 157 promotes angiogenesis in CAM assay and tube formation assay. BPC 157 accelerates the blood flow recovery and vessel number in rats with hind limb ischemia. BPC 157 up-regulates VEGFR2 expression in rats with hind limb ischemia and endothelial cell culture. BPC 157 promotes VEGFR2 internalization in association with VEGFR2-Akt-eNOS activation.BPC 157 promotes angiogenesis in CAM assay and tube formation assay. BPC 157 accelerates the blood flow recovery and vessel number in rats with hind limb ischemia. BPC 157 up-regulates VEGFR2 expression in rats with hind limb ischemia and endothelial cell culture. BPC 157 promotes VEGFR2 internalization in association with VEGFR2-Akt-eNOS activation.
- Subjects :
- 0301 basic medicine
Pathology
medicine.medical_specialty
Angiogenesis
media_common.quotation_subject
Neovascularization, Physiologic
Hindlimb
Pharmacology
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
In vivo
Ischemia
Drug Discovery
medicine
Human Umbilical Vein Endothelial Cells
Animals
Humans
Internalization
Genetics (clinical)
media_common
Tube formation
Chemistry
Kinase insert domain receptor
Vascular Endothelial Growth Factor Receptor-2
Rats
Up-Regulation
030104 developmental biology
030220 oncology & carcinogenesis
cardiovascular system
Molecular Medicine
Angiogenesis Inducing Agents
Signal transduction
Chickens
Blood Flow Velocity
Subjects
Details
- ISSN :
- 14321440
- Volume :
- 95
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Journal of molecular medicine (Berlin, Germany)
- Accession number :
- edsair.doi.dedup.....d08e1bedfe4b24b347398d28bee64c5a