Prognostic value of plasminogen activator inhibitor type 1 mRNA in microdissected glomeruli from transplanted kidneys.
BACKGROUND
Plasminogen activator inhibitor type 1 (PAI-1) exerts antifibrinolytic and profibrotic activities. Inside the glomerulus, PAI-1 is mainly synthesized by mesangial cells. We hypothesized that thrombin, via its receptor protease activated receptor type 1 (PAR-1), present on the membrane of glomerular cells, is an important mediator of PAI-1 synthesis.


METHODS
Using the technique of Peten et al., we microdissected the glomeruli of 23 kidney transplanted patients admitted in our department from 1993 to 1997, and we followed-up these patients for up to 5 years, with sometimes iterative renal biopsies. With this technique, we also microdissected the glomeruli of three patients who have had a nephrectomy for cancer (control patients). We investigated mRNA expression of the PAI-1, the thrombin receptor PAR-1, the alpha2 chain of type IV (alpha2 IV) collagen, and of a housekeeping gene (cyclophilin) by reverse transcription-polymerase chain reaction. The results were correlated with the renal function and the histological findings classified into acute rejection (9 biopsies), chronic rejection (22 biopsies), or normal (8 biopsies).


RESULTS
A significant up-regulation of PAI-1 and alpha2 IV collagen mRNA was observed in acute rejection (P<0.05) when compared to normal kidneys. A positive correlation exists between alpha2 IV collagen mRNA level and the degree of cellular infiltration. A negative correlation was found between the level of mRNA of PAR-1 and the degree of vascular thrombosis (P=0.005) and glomerulosclerosis (P=0.04). A positive correlation was found between the degradation of renal function and the mRNA level of PAI-1 at the time of the renal biopsy (P<0.05).


CONCLUSIONS
These results suggest that glomerular PAI-1 mRNA may be predictive of the long-term renal graft function.
Delarue
F
F
Département de Néphrologie A, Inserm U489, Association Claude Bernard, Hôpital Tenon, Paris, France.
Hertig
A
A
Alberti
C
C
Vigneau
C
C
Ammor
M
M
Berrou
J
J
Akposso
K
K
Peraldi
M N
MN
Rondeau
E
E
Sraer
J D
JD
D000293:Adolescent; D000328:Adult; D004210:Dissection; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D008866:Microsurgery; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism*; D013997:Time Factors
D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger