Cyclic AMP inhibits stretch-induced overexpression of fibronectin in glomerular mesangial cells

Eur J Pharmacol. 2002 Feb 22;437(3):113-22. doi: 10.1016/s0014-2999(01)01559-x.

Abstract

Glomerular hypertension is proposed to play an important role in the progression of various glomerular diseases. Glomerular mesangial cells are considered to be exposed to the stretch stress due to glomerular hypertension and are found to produce the excess amount of extracellular matrix (ECM) proteins including fibronectin when exposed to the mechanical stretch. Herein, we provide the evidence that cAMP-generating agents inhibit the stretch-induced overexpression of fibronectin through the inhibition of the stretch-induced activation of mitogen-activated protein kinases (MAPKs) in protein kinase-A-dependent manner. We also found that the mechanical stretch enhanced the binding of nuclear extracts to activator protein-1 (AP-1)-like sequences in the promoter region of rat fibronectin gene and this enhancement was also prevented by the cAMP-generating agent. These results indicate that the agents, which activate cAMP/protein kinase-A axis, may work protectively against the injury from glomerular hypertension in mesangial cells.

MeSH terms

  • Animals
  • Blotting, Northern
  • Blotting, Western
  • Bucladesine / metabolism
  • Bucladesine / pharmacology*
  • Carbazoles*
  • Cyclic AMP / metabolism
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Epoprostenol / analogs & derivatives*
  • Epoprostenol / metabolism
  • Epoprostenol / pharmacology*
  • Fibronectins / genetics*
  • Gene Expression Regulation / drug effects
  • Glomerular Mesangium / cytology
  • Glomerular Mesangium / drug effects*
  • Glomerular Mesangium / metabolism
  • Indoles / pharmacology
  • Male
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Nuclear Proteins / metabolism
  • Oligonucleotides / genetics
  • Oligonucleotides / metabolism
  • Protein Binding / drug effects
  • Pyrroles / pharmacology
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Mechanical
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism

Substances

  • Carbazoles
  • Enzyme Inhibitors
  • Fibronectins
  • Indoles
  • Nuclear Proteins
  • Oligonucleotides
  • Pyrroles
  • RNA, Messenger
  • Transcription Factor AP-1
  • beraprost
  • KT 5720
  • Bucladesine
  • Epoprostenol
  • Cyclic AMP
  • Mitogen-Activated Protein Kinases