Role of mesangial Factor V expression in crescent formation in rat experimental mesangioproliferative glomerulonephritis.
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.
Ono
Takahiko
T
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ono@u-shizuoka-ken.ac.jp
Liu
Ning
N
Makino
Toshiaki
T
Nogaki
Fumiaki
F
Nomura
Keiko
K
Muso
Eri
E
Shimizu
Fujio
F
Honda
Gisho
G
Kita
Toru
T
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology; D005165:Factor V / Q000032:analysis* / Q000276:immunology; D005337:Fibrin / Q000096:biosynthesis*; D005920:Glomerular Mesangium / Q000378:metabolism / Q000473:pathology*; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism / Q000473:pathology*; D008297:Male; D016253:Microscopy, Immunoelectron / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D000906:Antibodies; D012333:RNA, Messenger; D005165:Factor V; D005337:Fibrin