Role of PKC and TGF-beta receptor in glucose-induced proliferation of smooth muscle cells

Biochem Biophys Res Commun. 2001 Feb 16;281(1):71-7. doi: 10.1006/bbrc.2001.4310.

Abstract

The role of protein kinase C (PKC) and transforming growth factor (TGF)-beta in the proliferation of vascular smooth muscle cells (SMCs) under a high glucose condition was investigated. [3H]-thymidine incorporation under 20 mM glucose was significantly accelerated compared with that under 5.5 mM glucose, and this increase was inhibited by an anti-TGF-beta antibody or a PKC-beta specific inhibitor, LY333531. The amount of active and total TGF-beta1 in the conditioned media did not differ between 5.5 and 20 mM glucose. However, the expression of TGF-beta receptor type II under 20 mM glucose was significantly increased, but that of the TGF-beta receptor type I was not. This increased expression of the TGF-beta receptor type II was prevented by LY333531. These observations suggest that the increased expression of the TGF-beta receptor type II via PKC-beta plays an important role in the accelerated proliferation of SMCs under a high glucose condition, leading to the development of diabetic macroangiopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors, Type I*
  • Animals
  • Aorta / metabolism
  • Cell Division
  • Cells, Cultured
  • Culture Media, Conditioned / metabolism
  • DNA / biosynthesis
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Glucose / metabolism*
  • Glucose / pharmacology
  • Immunoblotting
  • Indoles / pharmacology
  • Maleimides / pharmacology
  • Muscle, Smooth / cytology*
  • Muscle, Smooth / metabolism*
  • Protein Kinase C / physiology*
  • Protein Serine-Threonine Kinases / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / metabolism
  • Receptors, Transforming Growth Factor beta / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Culture Media, Conditioned
  • Enzyme Inhibitors
  • Indoles
  • Maleimides
  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta
  • ruboxistaurin
  • DNA
  • Protein Serine-Threonine Kinases
  • Protein Kinase C
  • Activin Receptors, Type I
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • Tgfbr1 protein, rat
  • Glucose