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Id1-induced inhibition of p53 facilitates endothelial cell migration and tube formation by regulating the expression of beta1-integrin

  • Juhui Qiu
  • Guixue Wang
  • Jianjun Hu
  • Qin Peng
  • Yiming Zheng
Article

Abstract

The Id1 protein is critical for endothelial cell angiogenesis, and this function is particularly relevant to cancer development, cardiovascular disease, and wound healing. We hypothesized that Id1 enhanced migration and tubulogenesis by controlling the expression and function of p53. In this study, we examined cell migration following Id1 overexpression and silencing endothelial cells. The results showed that overexpression of Id1 enhanced cell migration and increased beta1-integrin expression, but inhibition of beta1-integrin blocked motility even in clones overexpressing Id1, suggesting that Id1 regulated motility through beta1-integrin. Further analysis revealed that p53, whose expression and distribution is regulated by Id1, was critical for cell migration, and may be involved in regulating the expression of beta1-integrin. Inhibiting p53 function using PFT-α, a functional inhibitor of p53, increased the expression of beta1-integrin and promoted cell migration even in Id1-silencing endothelial cells, demonstrating that the Id1 knockdowns induced inhibition of endothelial cell migration and the expression of beta1-integrin were controlled by p53. In addition, Id1–p53 pathway regulated the cytoskeleton formation and tubulogenesis. These results demonstrate that Id1-induced beta1-integrin expression in endothelial cells and the function of Id1 in cell migration and tubulogenesis are dependent on p53.

Keywords

Id1 Tubulogenesis Migration p53 Beta1-integrin 

Abbreviations

Id1

Inhibitors of differentiation

HLH

Helix-loop-helix

ECM

Extracellular matrix

HIF

Hypoxia inducible factor

HUVEC

Human umbilical vascular endothelial cells

RPMI 1640

Roswell Park Memorial Institute 1640

FBS

Fetal bovine serum

BSA

Bovine serum albumin

DAPI

6-Diamidino-2-phenylindole

Notes

Acknowledgments

This research program was supported by grants from the National Natural Science Foundation of China (30970721) and the Fundamental Research Funds for the Central Universities (CDJXS10 23 22 10).

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Juhui Qiu
    • 1
  • Guixue Wang
    • 1
  • Jianjun Hu
    • 1
  • Qin Peng
    • 1
  • Yiming Zheng
    • 1
  1. 1.Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Chongqing Engineering Laboratory in Vascular ImplantsBioengineering College of Chongqing UniversityChongqingPeople’s Republic of China

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