BMP-2 induces angiogenesis by provoking integrin α6 expression in human endothelial progenitor cells

被引：47

作者：

Chen, Wei-Cheng ^{[1
]}

Chung, Ching-Hu ^{[2
]}

Lu, Yung-Chang ^{[1
,2
]}

Wu, Min-Huan ^{[3
,4
]}

Chou, Po-Hsun ^{[1
]}

Yen, Juei-Yu ^{[1
]}

Lai, Yu-Wei ^{[5
,6
]}

Wang, Guo-Shou ^{[1
]}

Liu, Shih-Chia ^{[1
]}

Cheng, Jen-Kun ^{[1
,7
]}

Wu, Yih-Jer ^{[2
,8
]}

Yeh, Hung-I ^{[2
,8
]}

Wang, Li-Yu ^{[2
]}

Wang, Shih-Wei ^{[2
,9
]}

机构：

[1] Mackay Mem Hosp, Dept Orthopaed, Taipei, Taiwan

[2] Mackay Med Coll, Dept Med, 46,Sec 3,Zhongzheng Rd, New Taipei, Taiwan

[3] Tunghai Univ, Sports Recreat & Hlth Management Continuing Studi, Taichung, Taiwan

[4] Tunghai Univ, Phys Educ Off, Taichung, Taiwan

[5] Taipei City Hosp, Div Urol, Renai Branch, Taipei, Taiwan

[6] Natl Yang Ming Univ, Sch Med, Dept Urol, Taipei, Taiwan

[7] Mackay Mem Hosp, Dept Anesthesiol, Taipei, Taiwan

[8] Mackay Mem Hosp, Dept Internal Med, Taipei, Taiwan

[9] Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung, Taiwan

来源：

BIOCHEMICAL PHARMACOLOGY | 2018年 / 150卷

关键词：

Bone morphogenetic proteins-2; Endothelial progenitor cells; Integrin alpha 6; Angiogenesis; BONE MORPHOGENETIC PROTEIN-2; HUMAN CHONDROSARCOMA CELLS; PROSTATE-CANCER CELLS; NF-KAPPA-B; GROWTH-FACTOR; PROMOTES ANGIOGENESIS; TUMOR ANGIOGENESIS; IN-VITRO; HUMAN OSTEOSARCOMA; VASCULAR BIOLOGY;

D O I：

10.1016/j.bcp.2018.02.021

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Bone morphogenetic protein-2 (BMP-2) is a multifunctional cytokine, capable of governing several cellular functions, including proliferation, motility, differentiation, and angiogenesis. Circulating endothelial progenitor cells (EPCs) have been shown to facilitate tissue repair, postnatal neovascularization, and tumor associated angiogenesis. Nevertheless, the impact of BMP-2 on angiogenesis of human EPCs has largely remained a mystery. In this study, we found that BMP-2 promoted cell migration and tube formation of EPCs in a concentration dependent manner, indicating BMP-2 induced in vitro angiogenesis in human EPCs. Furthermore, BMP-2 significantly increased microvessel formation in Matrigel plug assay, and BMP-2 antagonist noggin prevented BMP2-induced in vivo angiogenesis. Mechanistic investigations showed BMP-2 profoundly induced the expression of Id-1 and integrin a6 as well as EPCs angiogenesis by activating PI3K/Akt and MEK/ERK signaling pathways. Moreover, knockdown of Id-1 and integrin a6 by siRNA transfection obviously attenuated BMP-2-indueced tube formation of EPCs. These results suggest that BMP-2 promotes angiogenesis in human EPCs through the activation of PI3K/Akt, MEK/ERK, and Id-1/integrin a6 signaling cascades. This is the first demonstration that BMP2 exhibits the angiogenesis property on human EPCs. BMP-2 might serve as the potential therapeutic target for treatment of angiogenesis-related diseases.

引用

页码：254 / 264

页数：11

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[41] NF-κB:: a new player in angiostatic therapy [J].