|Title / Titel||Novel Mechanisms in Chronic Allograft Rejection: Matrix Metalloproteinases (MMP) as Pro-inflammatory Mediators and Therapeutic Targets to Sustain Long-term Graft Survival|
|Abstract (PDF, 14 KB)|
|Original title / Originaltitel||Novel Mechanisms in Chronic Allograft Rejection: Matrix Metalloproteinases (MMP) as Pro-inflammatory Mediators and Therapeutic Targets to Sustain Long-term Graft Survival|
|Summary / Zusammenfassung||In accordance with previously published studies and our own preliminary results, we hypothesize the following:
· Matrix metalloproteinases (MMP) are up-regulated during the earlier decisive stages of chronic rejection, prior to the occurrence of end-stage tissue sclerosis. Thereby, MMP act as pro-inflammatory mediators and actively participate in tissue damage associated with chronic allograft rejection. Possible mechanisms are direct tissue injury, augmentation of excess cell proliferation/migration (e.g. vascular smooth muscle cells and fibroblasts), and facilitation of tissue invasion by extrinsic inflammatory cells (e.g. lymphocytes).
· MMP inhibition, for instance by the use of synthetic MMP inhibitors, ameliorates tissue damage during chronic allograft rejection.
|Publications / Publikationen||Berthier CC, Lods N, Joosten SA, van Kooten C, Leppert D, Lindberg RLP, Kappeler A, Raulf F, Sterchi EE, Lottaz D, Marti HP. Differential Regulation of Metzincins in Experimental Chronic Renal Allograft Rejection: Potential Markers and Novel Therapeutic Targets. In revision.Berthier CC, Weckbecker G, Raulf F, Kappeler A, Le Hir M, Marti HP. Acute rejection in experimental heart transplantation: effect of cyclosporine on matrix metalloproteinases and their inhibitors. Presented as abstract at the ATC winter conference, Banff, 2005. Manuscript in preparation.Lods N, Ferrari P, Frey FJ, Kappeler A, Berthier C, Vogt B, Marti HP: Angiotensin-converting enzyme inhibition but not angiotensin II receptor blockade regulates matrix metalloproteinase activity in patients with glomerulonephritis. J Am Soc Nephrol, 14(11):2861-2872, 2003.|
|Keywords / Suchbegriffe||MMP, kidney transplantation, rejection|
|Project leadership and contacts /
Projektleitung und Kontakte
|In collaboration with /
In Zusammenarbeit mit
|Duration of Project / Projektdauer||Jan 2003 to Dec 2005|