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Plasminogen and plasminogen activators protect against renal injury in crescentic glomerulonephritis.

Kitching AR, Holdsworth SR, Ploplis VA, Plow EF, Collen D, Carmeliet P, Tipping PG - J. Exp. Med. (1997)

Bottom Line: The plasminogen/plasmin system has the potential to affect the outcome of inflammatory diseases by regulating accumulation of fibrin and other matrix proteins.Deficiency of tPA, the predominant plasminogen activator expressed in glomeruli, also exacerbated disease. uPA deficiency reduced glomerular macrophage infiltration and did not significantly exacerbate disease. uPA receptor deficiency did not effect the expression of GN.These studies demonstrate that plasminogen plays an important role in protecting the glomerulus from acute inflammatory injury and that tPA is the major protective plasminogen activator.

View Article: PubMed Central - PubMed

Affiliation: Center for Inflammatory Diseases, Monash University, Department of Medicine, Monash Medical Centre, Victoria, Australia.

ABSTRACT
The plasminogen/plasmin system has the potential to affect the outcome of inflammatory diseases by regulating accumulation of fibrin and other matrix proteins. In human and experimental crescentic glomerulonephritis (GN), fibrin is an important mediator of glomerular injury and renal impairment. Glomerular deposition of matrix proteins is a feature of progressive disease. To study the role of plasminogen and plasminogen activators in the development of inflammatory glomerular injury, GN was induced in mice in which the genes for these proteins had been disrupted by homologous recombination. Deficiency of plasminogen or combined deficiency of tissue type plasminogen activator (tPA) and urokinase type plasminogen activator (uPA) was associated with severe functional and histological exacerbation of glomerular injury. Deficiency of tPA, the predominant plasminogen activator expressed in glomeruli, also exacerbated disease. uPA deficiency reduced glomerular macrophage infiltration and did not significantly exacerbate disease. uPA receptor deficiency did not effect the expression of GN. These studies demonstrate that plasminogen plays an important role in protecting the glomerulus from acute inflammatory injury and that tPA is the major protective plasminogen activator.

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Glomerular fibrin deposition and renal function (sCr) in  Plg−/−, WT (Plg), tPA−/−:uPA−/− and WT (tPA:uPA) mice (* indicates P <0.05, ‡P <0.01, ¶P <0.001, compared to appropriate WT control by unpaired t test).
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Figure 2: Glomerular fibrin deposition and renal function (sCr) in Plg−/−, WT (Plg), tPA−/−:uPA−/− and WT (tPA:uPA) mice (* indicates P <0.05, ‡P <0.01, ¶P <0.001, compared to appropriate WT control by unpaired t test).

Mentions: In contrast to the segmental fibrin deposition observed only within the glomerular tuft in WT mice (Fig. 1 B), Plg−/− and tPA−/−: uPA−/− mice developed extensive glomerular fibrin deposition within the glomerular tuft and in Bowman's space (Fig. 1, D and F). Semi-quantitative scoring of the extent of glomerular fibrin deposition confirmed that these differences were statistically significant compared to their WT controls (Fig. 2). Mice deficient in tPA also showed significant increases in glomerular fibrin deposition over WT (Fig. 3), though the extent of glomerular fibrin deposition did not reach that of the Plg−/− or the tPA−/−:uPA−/− mice. There were no significant changes in glomerular fibrin deposition in nephritic uPA−/− and uPAR−/− mice compared to WT mice.


Plasminogen and plasminogen activators protect against renal injury in crescentic glomerulonephritis.

Kitching AR, Holdsworth SR, Ploplis VA, Plow EF, Collen D, Carmeliet P, Tipping PG - J. Exp. Med. (1997)

Glomerular fibrin deposition and renal function (sCr) in  Plg−/−, WT (Plg), tPA−/−:uPA−/− and WT (tPA:uPA) mice (* indicates P <0.05, ‡P <0.01, ¶P <0.001, compared to appropriate WT control by unpaired t test).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196158&req=5

Figure 2: Glomerular fibrin deposition and renal function (sCr) in Plg−/−, WT (Plg), tPA−/−:uPA−/− and WT (tPA:uPA) mice (* indicates P <0.05, ‡P <0.01, ¶P <0.001, compared to appropriate WT control by unpaired t test).
Mentions: In contrast to the segmental fibrin deposition observed only within the glomerular tuft in WT mice (Fig. 1 B), Plg−/− and tPA−/−: uPA−/− mice developed extensive glomerular fibrin deposition within the glomerular tuft and in Bowman's space (Fig. 1, D and F). Semi-quantitative scoring of the extent of glomerular fibrin deposition confirmed that these differences were statistically significant compared to their WT controls (Fig. 2). Mice deficient in tPA also showed significant increases in glomerular fibrin deposition over WT (Fig. 3), though the extent of glomerular fibrin deposition did not reach that of the Plg−/− or the tPA−/−:uPA−/− mice. There were no significant changes in glomerular fibrin deposition in nephritic uPA−/− and uPAR−/− mice compared to WT mice.

Bottom Line: The plasminogen/plasmin system has the potential to affect the outcome of inflammatory diseases by regulating accumulation of fibrin and other matrix proteins.Deficiency of tPA, the predominant plasminogen activator expressed in glomeruli, also exacerbated disease. uPA deficiency reduced glomerular macrophage infiltration and did not significantly exacerbate disease. uPA receptor deficiency did not effect the expression of GN.These studies demonstrate that plasminogen plays an important role in protecting the glomerulus from acute inflammatory injury and that tPA is the major protective plasminogen activator.

View Article: PubMed Central - PubMed

Affiliation: Center for Inflammatory Diseases, Monash University, Department of Medicine, Monash Medical Centre, Victoria, Australia.

ABSTRACT
The plasminogen/plasmin system has the potential to affect the outcome of inflammatory diseases by regulating accumulation of fibrin and other matrix proteins. In human and experimental crescentic glomerulonephritis (GN), fibrin is an important mediator of glomerular injury and renal impairment. Glomerular deposition of matrix proteins is a feature of progressive disease. To study the role of plasminogen and plasminogen activators in the development of inflammatory glomerular injury, GN was induced in mice in which the genes for these proteins had been disrupted by homologous recombination. Deficiency of plasminogen or combined deficiency of tissue type plasminogen activator (tPA) and urokinase type plasminogen activator (uPA) was associated with severe functional and histological exacerbation of glomerular injury. Deficiency of tPA, the predominant plasminogen activator expressed in glomeruli, also exacerbated disease. uPA deficiency reduced glomerular macrophage infiltration and did not significantly exacerbate disease. uPA receptor deficiency did not effect the expression of GN. These studies demonstrate that plasminogen plays an important role in protecting the glomerulus from acute inflammatory injury and that tPA is the major protective plasminogen activator.

Show MeSH
Related in: MedlinePlus