Angiopoietin 1, PDGF-B, and TGF-beta gene regulation in endothelial cell and smooth muscle cell interaction

J Cell Biochem. 2004 Feb 15;91(3):584-93. doi: 10.1002/jcb.10718.

Abstract

The vascular wall is mainly composed of endothelial cells (ECs) and smooth muscle cells (SMCs). The crosstalking between these two cell types is critical in the vascular maturation process. Genetic studies suggest that the Tie2/angiopoietin 1 (Ang1) pathway regulates vascular remodeling. However, the molecular mechanism is unclear. PDGF is a potent chemoattractant for SMCs, and TGF-beta regulates SMC differentiation. Here, we examined gene regulation. PDGF-B stimulation upregulated Ang1 expression in SMCs through the PI3K and PKC pathways. PDGF-B stimulation also produced an acute induction of TGF-beta expression in SMCs through the MAPK/ERK pathway. Interestingly, TGF-beta negatively regulated Ang1 expression induced by the PDGF-B stimulation in SMCs. Reciprocally, we observed that stimulation of ECs with either Ang1 or TGF-beta slightly downregulated PDGF expression. A combination of both TGF-beta with Ang1 produced much stronger downregulation of PDGF. Our data showed complex gene regulations that include both positive and negative regulations between ECs and SMCs to maintain vascular homeostasis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiopoietin-1 / genetics
  • Angiopoietin-1 / metabolism
  • Angiopoietin-1 / pharmacology
  • Becaplermin
  • Blotting, Northern
  • Blotting, Western
  • Cell Communication / physiology*
  • Cell Differentiation / physiology
  • Cell Line
  • Down-Regulation
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism*
  • Pericytes / physiology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Platelet-Derived Growth Factor / genetics
  • Platelet-Derived Growth Factor / metabolism
  • Platelet-Derived Growth Factor / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Proto-Oncogene Proteins c-sis
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Receptor, TIE-2 / metabolism
  • Signal Transduction / physiology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology
  • Umbilical Veins / cytology
  • Up-Regulation

Substances

  • Angiopoietin-1
  • Enzyme Inhibitors
  • Intercellular Signaling Peptides and Proteins
  • Phosphoinositide-3 Kinase Inhibitors
  • Plasminogen Activator Inhibitor 1
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-sis
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Becaplermin
  • Receptor, TIE-2
  • Protein Kinase C
  • Mitogen-Activated Protein Kinase Kinases