Fibrin deposition is often noted in mesangial areas in active types of human mesangioproliferative glomerulonephritis; IgA nephropathy or Henoch-Schonlein purpura nephritis.1,2In vivo, mesangial cells are provided with various coagulation factors from blood circulation through fenestration of glomerular capillary endothelium. Factor V in its active form (Va) officiates as a membrane-bound cofactor to factor Xa, forming prothrombinase complex Xa/Va, which converts prothrombin to thrombin. In the present study, to clarify the contribution of factor V in intramesangial coagulation, mesangial factor V expression and its relationship to mesangial proliferation was investigated. Cross-linked fibrin (XFb) was detected in renal biopsy specimens from the patients of IgA nephropathy using anti-d-dimer antibody combined with plasmin exposure,1 and factor V was detected with rabbit antibody against human factor V. The expression of factor V mRNA was assessed by in situ hybridization in relation to the simultaneous antigen staining of alpha-smooth muscle actin (α-SMA). For in vitro study, cultured human mesangial cells (MCs) were stimulated with TNF-α (100 U/mL), and immunocytochemically stained the factor V protein, or evaluated by Western blot analysis. In another experiment, starved MCs were further incubated in combination with factor Xa, prothrombin, fibrinogen and factor XIII, and fibrin production on MCs was assessed. In a blocking test using an antibody against factor V, suppression of fibrin production was evaluated. XFb deposition and factor V expression were markedly correlated with disease activity (Table 1). By in situ hybridization, factor V mRNA was detected mainly in the mesangial cells which were positive for α-SMA, and partly in endothelial cells. In vitro study revealed that factor V expression was elevated time-dependently after TNF-α stimulation (P < 0.01), and that fibrin production on TNF-α-stimulated MCs was increased (P < 0.0001), and inhibited by the addition of antifactor V antibody (P < 0.01). Table 1. Relationship of XFb deposition and factor V expression to histological and immunohistochemical findings P value vs XFb P value vs factor V Mesangial cell proliferation 0.02 0.04 Necrotizing lesion 0.02 0.03 Cellular crescent 0.02 0.03 Interstitial mononuclear infiltrate 0.04 0.07 Activity index 0.005 0.008 In conclusion, factor V is expressed in mesangial cells after stimulation by inflammation, and may exert procoagulant activity in cooperation with exogenous factor Xa, leading to intramesangial coagulation in IgA nephropathy.