Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation

Ming Jer Hsieh, Hsien Ta Liu, Chao Nin Wang, Hsiu Yun Huang, Yuling Lin, Yu Shien Ko, Jong Shyan Wang, Vincent Hung Shu Chang, Jong Hwei S Pang

研究成果: 雜誌貢獻文章

16 引文 (Scopus)

摘要

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. Key message: 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.
原文英語
頁(從 - 到)323-333
頁數11
期刊Journal of Molecular Medicine
95
發行號3
DOIs
出版狀態已發佈 - 三月 1 2017

指紋

Vascular Endothelial Growth Factor Receptor-2
Up-Regulation
Therapeutics
Extremities
Chorioallantoic Membrane
Ischemia
Endothelial Cells
BPC 157
Cell Culture Techniques
Muscles

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

引用此文

Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation. / Hsieh, Ming Jer; Liu, Hsien Ta; Wang, Chao Nin; Huang, Hsiu Yun; Lin, Yuling; Ko, Yu Shien; Wang, Jong Shyan; Chang, Vincent Hung Shu; Pang, Jong Hwei S.

於: Journal of Molecular Medicine, 卷 95, 編號 3, 01.03.2017, p. 323-333.

研究成果: 雜誌貢獻文章

Hsieh, Ming Jer ; Liu, Hsien Ta ; Wang, Chao Nin ; Huang, Hsiu Yun ; Lin, Yuling ; Ko, Yu Shien ; Wang, Jong Shyan ; Chang, Vincent Hung Shu ; Pang, Jong Hwei S. / Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation. 於: Journal of Molecular Medicine. 2017 ; 卷 95, 編號 3. 頁 323-333.
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abstract = "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. Key message: 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.",
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author = "Hsieh, {Ming Jer} and Liu, {Hsien Ta} and Wang, {Chao Nin} and Huang, {Hsiu Yun} and Yuling Lin and Ko, {Yu Shien} and Wang, {Jong Shyan} and Chang, {Vincent Hung Shu} and Pang, {Jong Hwei S}",
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AU - Hsieh, Ming Jer

AU - Liu, Hsien Ta

AU - Wang, Chao Nin

AU - Huang, Hsiu Yun

AU - Lin, Yuling

AU - Ko, Yu Shien

AU - Wang, Jong Shyan

AU - Chang, Vincent Hung Shu

AU - Pang, Jong Hwei S

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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. Key message: 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.

AB - 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. Key message: 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.

KW - Angiogenesis

KW - BPC 157

KW - CAM assay

KW - Hind limb ischemia

KW - Tube formation

KW - VEGFR2

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