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Orphan nuclear receptor TR3/Nur77 differentially regulates the expression of integrins in angiogenesis

Taiyang Ye1, Jin Peng2, Xin Liu3

  • 1Center for Vascular Biology Research and Division of Gastroenterology, Departments of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Department of Obstetrics & Gynecology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200127, PR China.

Microvascular Research
|November 5, 2018
PubMed

Insights

Orphan nuclear receptor TR3/Nur77 regulates pathological angiogenesis by altering integrin expression. Targeting TR3/Nur77 offers a therapeutic strategy for diseases involving abnormal blood vessel formation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Pathological angiogenesis is implicated in numerous diseases.
  • The orphan nuclear receptor TR3/Nur77 (Nur77) was previously identified as a key regulator of angiogenesis.
  • The precise molecular mechanisms underlying TR3/Nur77's role in angiogenesis require further elucidation.

Purpose of the Study:

  • To investigate the molecular mechanisms by which TR3/Nur77 regulates angiogenesis.
  • To identify specific integrins modulated by TR3/Nur77 and their roles in endothelial cell functions.
  • To explore the transcriptional regulation of integrins by TR3/Nur77.

Main Methods:

  • Analysis of integrin expression profiles in endothelial cells under TR3/Nur77 influence.
  • Functional assays (proliferation, adhesion, migration) using specific integrin knockdown (shRNA).
  • Reporter assays and DNA-protein interaction studies to assess transcriptional regulation by TR3/Nur77.

Main Results:

  • TR3/Nur77 modulated the expression of specific integrins: increased α1 and β5, decreased α2 and β3.
  • Integrin α1 influenced proliferation and adhesion; β5 affected migration, proliferation, and adhesion; α2 impacted all three functions; β3 had no role.
  • TR3/Nur77 transcriptionally regulated integrins α1, α2, β3, and β5, directly interacting with the integrin α1 promoter.

Conclusions:

  • TR3/Nur77 regulates angiogenesis through differential modulation of integrin expression and function.
  • TR3/Nur77 directly controls integrin transcription, highlighting a novel regulatory mechanism.
  • These findings reinforce TR3/Nur77 as a promising therapeutic target for pathological angiogenesis.
Keywords:
AngiogenesisIntegrinMigrationProliferationPromoterTR3/Nur77

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