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Published on: August 19, 2020
Role of mesangial Factor V expression in crescent formation in rat experimental mesangioproliferative
Takahiko Ono1, Ning Liu, Toshiaki Makino
1Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ono@u-shizuoka-ken.ac.jp
Abstract:
It has been suggested that fibrin deposition participates in the development of crescents in active glomerulonephritis (GN). In human IgA nephropathy, which is a common form of mesangioproliferative GN (MsPGN), crescent formation is occasionally observed in active disease, leading to end-stage renal failure. Factor V is a membrane-bound potent cofactor for the conversion of prothrombin to thrombin by Factor Xa. An in vivo study was conducted to clarify the contribution of local fibrin production to crescent formation in MsPGN through mesangial Factor V expression. Wistar rats were injected intravenously with rabbit anti-rat thymocyte serum. Three days after injection, mesangiolysis with intense mesangial Factor V expression was observed and immunoelectron microscopy revealed fibrin localization in mesangiolytic lesions, which had spread into the glomerular basement membrane adjacent to the destroyed mesangium, accompanied by clots in Bowman's space. Marked glomerular fibrin deposition, together with its deposition in Bowman's space and cellular crescent formation, was noted with mesangial proliferation on day 8. Specific bands for Factor V mRNA were also detected from isolated glomeruli. Fibrin deposition and cellular crescent formation were significantly suppressed by treatment with anti-Factor V antibody. These results suggest that local fibrin production, following mesangial Factor V expression, together with mesangiolysis that spreads to the adjacent glomerular basement membrane, plays a role in crescent formation in MsPGN.
Insights
Fibrin deposition contributes to crescent formation in mesangioproliferative glomerulonephritis (MsPGN). Blocking Factor V reduced fibrin and crescent development, suggesting a key role for local fibrin production in this kidney disease.
Area of Science:
- Nephrology
- Pathology
- Immunology
Background:
- Crescent formation in active glomerulonephritis (GN) is linked to fibrin deposition.
- IgA nephropathy, a common mesangioproliferative GN (MsPGN), can exhibit crescent formation, potentially leading to renal failure.
- Factor V is crucial for thrombin generation, a precursor to fibrin.
Purpose of the Study:
- To investigate the role of local fibrin production in MsPGN crescent formation.
- To examine the contribution of mesangial Factor V expression to this process.
Main Methods:
- An in vivo Wistar rat model of MsPGN was induced using anti-thymocyte serum.
- Mesangial Factor V expression, fibrin localization, and glomerular changes were assessed via immunoelectron microscopy.
- Factor V mRNA levels and the effect of anti-Factor V antibody treatment were evaluated.
Main Results:
- Mesangiolysis with intense mesangial Factor V expression and fibrin deposition in glomeruli and Bowman's space were observed.
- Fibrin deposition and cellular crescent formation were significantly reduced by anti-Factor V antibody treatment.
- Factor V mRNA was detected in isolated glomeruli, confirming local production.
Conclusions:
- Local fibrin production, mediated by mesangial Factor V expression and mesangiolysis, contributes to crescent formation in MsPGN.
- Targeting Factor V may offer a therapeutic strategy for managing crescentic MsPGN.
