TGF-beta 1 signaling controls retinal pericyte contractile protein expression

Microvasc Res. 2003 Nov;66(3):190-6. doi: 10.1016/s0026-2862(03)00055-4.

Abstract

To define the role of transforming growth factor-beta 1 (TGF-beta 1) in modulating pericyte contractile phenotype, we have ablated the TGF-beta signaling pathway by infection with a retrovirus bearing a TGF-beta type II receptor with a truncated C-terminal intracellular kinase domain (DNT beta RII). While TGF-beta 1 blocks pericyte proliferation and induces the expression of vascular smooth muscle contractile proteins in wild-type pericytes, DNT beta RII-bearing pericytes are neither growth inhibited by TGF-beta 1 nor do they accumulate alpha-smooth muscle actin (alpha-SMA) mRNA or protein. TGF-beta 1 induces expression of the myogenic transcription factor myf-5 and the cyclin-dependent kinase inhibitor p27; we show that these signaling pathways are disrupted in the DNT beta RII-bearing pericytes. These observations demonstrate that the TGF-beta 1 signaling pathway controls pericyte growth state and contractile phenotype.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Animals
  • Blotting, Western
  • Cattle
  • Cell Differentiation
  • Cell Division
  • Cells, Cultured
  • DNA Primers / pharmacology
  • DNA-Binding Proteins*
  • Fluorescent Antibody Technique, Indirect
  • Gene Expression Regulation*
  • Genes, Dominant
  • Mice
  • Microfilament Proteins / metabolism
  • Microscopy, Fluorescence
  • Muscle Proteins / metabolism
  • Muscle, Smooth / metabolism
  • Muscle, Smooth, Vascular / cytology
  • Mutation
  • Myogenic Regulatory Factor 5
  • Pericytes / metabolism*
  • Phenotype
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases
  • RNA, Messenger / metabolism
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / metabolism
  • Retina / cytology
  • Retina / metabolism*
  • Retroviridae / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction*
  • Trans-Activators*
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta1

Substances

  • Actins
  • DNA Primers
  • DNA-Binding Proteins
  • Microfilament Proteins
  • Muscle Proteins
  • Myf5 protein, mouse
  • Myogenic Regulatory Factor 5
  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta
  • Tagln protein, mouse
  • Tgfb1 protein, mouse
  • Trans-Activators
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Protein-Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II