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Nitric oxide modulates the synthesis of extracellular matrix proteins in cultured rat mesangial cells
H Trachtman1, S Futterweit, P Singhal
1Department of Pediatrics and Medicine, Schneider Children's Hospital, New Hyde Park, NY.
Abstract:
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.
Insights
Nitric oxide (NO) influences extracellular matrix production in kidney mesangial cells. This study shows NO reduces collagen and fibronectin but increases laminin, potentially limiting glomerulosclerosis in kidney diseases.
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Nitric oxide (NO) is a key mediator in inflammatory responses.
- Mesangial cells synthesize NO and are implicated in glomerular injury.
- The role of NO in extracellular matrix (ECM) production by mesangial cells is not fully understood.
Purpose of the Study:
- To investigate the effect of NO on extracellular matrix production in cultured rat mesangial cells.
- To determine if NO modulates the synthesis of collagen, fibronectin, and laminin.
Main Methods:
- Cultured rat mesangial cells were stimulated to release NO using gamma-interferon and lipopolysaccharide.
- Production of collagen, fibronectin, and laminin was quantified.
- The effects were assessed with and without L-NAME, an inhibitor of inducible nitric oxide synthase.
Main Results:
- NO stimulation significantly reduced collagen production by 35% and fibronectin by 48%.
- Laminin synthesis was significantly increased two-fold.
- These changes were reversed by L-NAME, confirming the role of NO.
Conclusions:
- Nitric oxide (NO) directly regulates extracellular matrix synthesis in mesangial cells.
- Increased renal NO production in glomerular diseases may reduce matrix accumulation.
- This suggests a protective role for NO against glomerulosclerosis progression.