title: Prognostic value of plasminogen activator inhibitor type 1 mRNA in microdissected glomeruli from transplanted kidneys.
abstract: 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.
authors.affiliation: Département de Néphrologie A, Inserm U489, Association Claude Bernard, Hôpital Tenon, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Delarue
authors.forename: A
authors.initials: A
authors.lastname: Hertig
authors.forename: C
authors.initials: C
authors.lastname: Alberti
authors.forename: C
authors.initials: C
authors.lastname: Vigneau
authors.forename: M
authors.initials: M
authors.lastname: Ammor
authors.forename: J
authors.initials: J
authors.lastname: Berrou
authors.forename: K
authors.initials: K
authors.lastname: Akposso
authors.forename: M N
authors.initials: MN
authors.lastname: Peraldi
authors.forename: E
authors.initials: E
authors.lastname: Rondeau
authors.forename: J D
authors.initials: JD
authors.lastname: Sraer
mesh_terms: 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
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger