Signal transduction in rat vascular smooth muscle cells: control of osmotically induced aldose reductase expression by cell kinases and phosphatases

Biochem Biophys Res Commun. 1999 Feb 5;255(1):12-6. doi: 10.1006/bbrc.1998.0137.


We have studied the osmotically induced gene expression (measured as chloramphenicol acetyl transferase (CAT) reporter gene expression) in rat smooth muscle cell primary cultures (rSMC), under the control of osmotic response elements (ORE). It was found that osmotically induced gene expression is sensitive to signal transduction inhibitors and activators. In particular, protein kinase C inhibition by calphostin C prevented gene expression by osmotic response. On the other hand, receptor tyrosine kinase inhibition has been shown to produce an enhancement of gene expression. This suggests that tyrosine kinase receptor activation exerts an inhibitory action on ORE induced gene expression. Gene expression was also induced by treating cells with PD098059, a specific inhibitor of mitogen-activated protein kinase kinase. Moreover, the same inhibitors and activators have been shown to affect the hyperosmosis induced expression of aldose reductase gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Reductase / physiology*
  • Animals
  • Cells, Cultured
  • Enzyme Inhibitors
  • Flavonoids / pharmacology
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Enzymologic / physiology
  • Muscle, Smooth, Vascular / physiology*
  • Osmotic Pressure
  • Phosphoric Monoester Hydrolases / physiology*
  • Protein Kinases / physiology*
  • Rats
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*


  • Enzyme Inhibitors
  • Flavonoids
  • Aldehyde Reductase
  • Protein Kinases
  • Phosphoric Monoester Hydrolases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one