Nitric oxide modulates the synthesis of extracellular matrix proteins in cultured rat mesangial cells.
Nitric oxide (NO) is an important effector molecule of the inflammatory response. It is synthesized by mesangial cells and has been proposed to contribute to glomerular injury in various disease states. We studied whether NO modulates extracellular matrix production in cultured rat mesangial cells. Stimulation of rat mesangial cell NO release with gamma-interferon and lipopolysaccharide resulted in reduced production of collagen (by 35%) fibronectin (by 48%) (P < 0.05). In contrast, laminin synthesis was enhanced two-fold by the same maneuver (P < 0.05). These changes were reversed by the addition of L-NAME, a selective inhibitor of inducible nitric oxide synthase. This is the first demonstration that NO regulates the synthesis of extracellular matrix by mesangial cells. The results indicate that increased renal production of NO in glomerular diseases may attenuate the production and accumulation of matrix proteins and limit the severity of glomerulosclerosis.
Department of Pediatrics and Medicine, Schneider Children's Hospital, New Hyde Park, NY.
H
H
Trachtman
S
S
Futterweit
P
P
Singhal
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D005353:Fibronectins / Q000096:biosynthesis; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D007797:Laminin / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D009573:Nitrites / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D008070:Lipopolysaccharides; D009573:Nitrites; D011994:Recombinant Proteins; D009569:Nitric Oxide; D007371:Interferon-gamma; D003094:Collagen; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester