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Mesangial factor V expression colocalized with fibrin deposition in IgA nephropathy
1Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Japan.
Background:
Factor V in its active form (Va) plays a key role at the termination of the intrinsic coagulation pathway, serving as a membrane-bound cofactor for the conversion of prothrombin to thrombin by factor Xa. Cross-linked fibrin (XFb) is often observed in mesangial areas in active types of human glomerulonephritis. In this study, to clarify contribution of factor V in intramesangial coagulation, mesangial factor V expression and its relationship to mesangial proliferation and fibrin deposition in IgA nephropathy (IgAN) were investigated.
Methods:
Twenty-two patients with IgAN were studied. XFb was detected in renal biopsy specimens using anti-d-dimer antibody combined with plasmin exposure, and factor V was detected with rabbit antibody against human factor V. Double-labeling immunohistochemistry was used to investigate the relationship of the glomerular distribution of factor V to XFb. The relationship of factor V staining to the activity index or XFb deposition was evaluated. The expression of factor V mRNA was assessed by in situ hybridization in relationship to the antigen staining of alpha-smooth muscle actin (alpha-SMA). The ultrastructural distribution of factor V in glomeruli was studied by immunoelectron microscopy.
Results:
XFb and factor V were observed in the mesangium and along capillary loops in seven and nine specimens, respectively. Factor V had intense, frequent expression in the proliferating and necrotizing areas, showing a significant relationship to XFb (P < 0.05). Furthermore, XFb deposition and factor V expression were markedly correlated with disease activity (P = 0.005 and P = 0.008, respectively). By double-labeling experiments, XFb and factor V were often seen colocalized in mesangial areas of the glomeruli, which showed necrotizing lesions and/or intense cellular proliferation. By in situ hybridization, factor V mRNA was detected mainly in the mesangial cells, which were positive for alpha-SMA, and partly in the endothelial cells. By immunoelectron microscopy, factor V presence was confirmed in the mesangium and endothelium.
Conclusion:
The present findings suggest that factor V is strongly expressed in mesangial cells in active IgAN accompanied with mesangial proliferation and may exert procoagulant activity, leading to intramesangial coagulation.
Insights
Factor V is highly expressed in active IgA nephropathy (IgAN) with mesangial proliferation. This suggests factor V contributes to intramesangial coagulation in IgAN patients.
Area of Science:
- Nephrology
- Hematology
- Immunology
Background:
- Factor V (FV) is crucial in coagulation, acting as a cofactor for thrombin generation.
- Cross-linked fibrin (XFb) deposition is observed in active glomerulonephritis, particularly IgA nephropathy (IgAN).
Purpose of the Study:
- To investigate mesangial factor V expression in IgAN.
- To determine the relationship between factor V, mesangial proliferation, and fibrin deposition in IgAN.
Main Methods:
- Studied 22 IgAN patients using immunohistochemistry for XFb and factor V.
- Assessed factor V mRNA via in situ hybridization and ultrastructural localization by immunoelectron microscopy.
- Correlated factor V and XFb with disease activity and mesangial proliferation.
Main Results:
- Factor V and XFb were found in mesangial areas and along capillary loops.
- Factor V expression strongly correlated with XFb deposition (P < 0.05) and disease activity (P = 0.008).
- Factor V and XFb colocalized in areas of mesangial proliferation and necrotizing lesions.
Conclusions:
- Factor V is significantly expressed in mesangial cells during active IgAN.
- Factor V expression is linked to mesangial proliferation and XFb deposition.
- Findings suggest factor V contributes to intramesangial coagulation in IgAN.