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- Title
Expression of tissue type plasminogen activator and type 1 plasminogen activator inhibitor, and persistent fibrin deposition in chronic renal allograft failure.
- Authors
Yiming Wang; Pratt, Julian R.; Hartley, Barrie; Evans, Beryl; Lyna Zhang; Sacks, Steven H.
- Abstract
Persistent fibrin deposition has been observed in kidneys undergoing chronic rejection, and has been suggested to contribute to the obliteration of the vasculature in these grafts. The mechanisms leading to it are not clear. Fibrinolysis, the process to remove fibrin in tissues, is initiated by tissue type plasminogen activator (tPA) and suppressed by type 1 plasminogen activator inhibitor (PAI-1). To investigate their roles in chronic rejection and fibrin deposition, we serially examined the expression of tPA and PM-1 in an unmodified chronic rejection model, using a Fisher 344 to Lewis rat renal transplant, at 0, 2, 4, 6, 10, 12, 16 and 20 weeks post-transplantation (<em>N</em> = 4 rats/time point in each group). We also analyzed fibrin deposition and the development of chronic changes in the grafts. Our results show that tPA was up-regulated only in the acute phase of rejection (<em>P</em> < 0.05), whereas PAI-1 was induced and persistently expressed during the progressive phase of chronic rejection, together with persistent fibrin deposition in the grafts. Immunohistochemistry showed PAI-1 was mainly localized to the damaged/proliferative vascular intima. The results suggest that persistent induction of PAI-1 may be responsible for the continuance of fibrin deposition, which is associated with irreversible damage and chronic graft loss.
- Subjects
TISSUE plasminogen activator; BLOOD coagulation; TISSUE banks; IMMUNOHISTOCHEMISTRY; PROCUREMENT of organs, tissues, etc.; URINARY organs
- Publication
Kidney International, 1997, Vol 52, Issue 2, p371
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/ki.1997.343