4.6 Article

The influence of receptor activity-modifying protein-1 overexpression on angiogenesis in mouse brain capillary endothelial cells

Journal

JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 120, Issue 6, Pages 10087-10096

Publisher

WILEY
DOI: 10.1002/jcb.28292

Keywords

adrenomedullin 2; angiogenesis; mouse brain capillary endothelial cells; receptor activity-modifying protein-1; vascular endothelial growth factor

Funding

  1. National Natural Science Foundation of China [81701007, 81571008]
  2. China Postdoctoral Science Foundation [2018M631091]
  3. Youth Science Foundation of West China Hospital of Stomatology of Sichuan University [201611]
  4. Fundamental Research Funds for the Central Universities [2017SCU12056, 2018SCUH0006]
  5. Sichuan Science and Technology Program [2018RZ0087]

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Receptor activity-modifying protein-1 (RAMP1) is highly expressed in the heart and vasculature, indicating that it might be related to the vascular system. However, the effects of RAMP1 on angiogenesis and the intrinsic mechanisms underlying this process remain unclear. Here, we verified that RAMP1 is a critical regulator of angiogenesis in a mouse brain capillary endothelial cell line (bEnd.3). We first constructed a RAMP1 overexpression lentiviral vector system and stably transfected bEnd.3 cells. We further showed that RAMP1 overexpression could lead to bEnd.3 migration and capillary tube formation in Matrigel without exogenous calcitonin gene-related peptide (CGRP) treatment. At the same time, RAMP1 overexpression had little effect on proliferation. More importantly, vascular endothelial growth factor (VEGF) and CGRP expression levels were not significantly higher in RAMP1-overexpressing cells than in control cells (P>0.05), indicating that RAMP1 did not function through upregulating VEGF or CGRP expression in bEnd.3 cells. Strikingly, RAMP1 transfection increased adrenomedullin 2 (AM2) expression levels (P<0.05). Taken together, these data contribute to a better understanding of the molecular mechanisms of RAMP1 in angiogenesis.

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