Telomere shortening and cellular senescence in a model of chronic renal allograft rejection

Joosten, S.A., van Ham, V., Nolan, C.E., Borrias, M.C., Jardine, A.G. , Shiels, P.G. , van Kooten, C. and Paul, L.C. (2003) Telomere shortening and cellular senescence in a model of chronic renal allograft rejection. American Journal of Pathology, 162(4), pp. 1305-1312. (doi:10.1016/S0002-9440(10)63926-0)

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Abstract

Cellular senescence has been suggested to play a role in the deterioration of renal graft function and has been linked to telomere shortening. We have investigated markers of cellular senescence in the F344 to LEW rat model of chronic renal transplant rejection. Syngeneic and LEW to F344 transplants were used as controls. Substantial telomere shortening was observed in all transplants, including allogeneic and syngeneic grafts from day 7 post-transplant onwards. Ischemia of native F344 kidneys was already sufficient to induce telomere shortening. It is known that shortened telomeres can activate cell cycle regulators, such as p21 and p16. Accordingly, all cases showed a transient p21 increase, with a maximum at day 7 and a sustained expression of p16. Importantly, senescence-associated beta-galactosidase staining, a cytological marker for senescence, was only observed in tubular epithelial cells of chronically rejecting F344 allografts from day 30 post-transplantation onwards. Long-term surviving LEW allografts or syngeneic F344 grafts were negative for senescence-associated beta-galactosidase. In conclusion, ischemia during transplantation results in telomere shortening and subsequent activation of p21 and p16, whereas senescence-associated beta-galactosidase staining is only present in chronically rejecting kidney grafts.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Paul, Dr Lorna and Shiels, Professor Paul and Jardine, Professor Alan
Authors: Joosten, S.A., van Ham, V., Nolan, C.E., Borrias, M.C., Jardine, A.G., Shiels, P.G., van Kooten, C., and Paul, L.C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Nursing and Health Care
Journal Name:American Journal of Pathology
Publisher:American Society for Investigative Pathology
ISSN:0002-9440
ISSN (Online):1525-2191
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