title: The biological effects and mechanisms of calcitonin gene-related peptide on human endothelial cell.
abstract: BACKGROUND
  Calcitonin gene-related peptide (CGRP) is a neuropeptide distributed in bone tissue involved in bone remodeling. Previously we demonstrated that CGRP can promote proliferation and migration of endothelial cells, relating to the expression of vascular endothelial growth factor (VEGF) and focal adhesion kinase (FAK).
  
  
  METHODS
  CGRP1 receptor expression in human umbilical vein endothelial cells (HUVECs) was examined by immunofluorescence microscopy and real-time PCR. Tube formation was measured by a Matrigel tube formation assay. VEGF protein and mRNA levels were quantified by ELISA and real-time PCR, respectively. The expression of VEGF receptor 1 (FLT1) and VEGF receptor 2 (KDR) were measured by real-time PCR and immunoblotting assays.
  
  
  RESULTS
  CGRP significantly induced vascular tube formation of outgrowth HUVECs in a Matrigel. The expression of FLT and KDR were significantly increased by CGRP, and CGRP enhanced the expression of CGRP1 receptors. Compared to the known angiogenesis regulator VEGF(165), CGRP had an equal or stronger effect on migration and tube formation, but not on proliferation of endothelial cells. The upregulation of calcitonin receptor-like receptor (CRLR), FAK, VEGF and its two main receptors (FLT1, KDR) by CGRP was also more pronounced than that obtained by VEGF(165).
  
  
  CONCLUSIONS
  It is concluded that CGRP is a strong proangiogenic growth factor, thereby contributing to bone development and remodeling by promoting angiogenesis.
authors: Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Yonghua
authors: Y
authors: Tuo
authors: Xiaolei
authors: X
authors: Guo
authors: Xinxin
authors: X
authors: Zhang
authors: Zhao
authors: Z
authors: Wang
authors: Jian
authors: J
authors: Zhou
authors: Liheng
authors: L
authors: Xia
authors: Yongtao
authors: Y
authors: Zhang
authors: Jun
authors: J
authors: Wen
authors: Dan
authors: D
authors: Jin
mesh_terms: D016723:Bone Remodeling / Q000235:genetics*; D002116:Calcitonin / Q000235:genetics / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics*; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018919:Neovascularization, Physiologic; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: C000606589:CALCA protein, human; D011498:Protein Precursors; D042461:Vascular Endothelial Growth Factor A; D002116:Calcitonin; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015740:Calcitonin Gene-Related Peptide