Genetic profiling of aortic allografts: prothymosin alpha as potential target?

Summary Transplant arteriosclerosis is the result of intima proliferation in large vessels upon organ transplantation. Obliteration of the vascular lumen will ultimately lead to ischemia and late graft failure. Gene array analysis was performed to identify factors involved in the pathogenesis of tra...

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Bibliographic Details
Published in:Transplant international 2005-08, Vol.18 (8), p.1010-1015
Main Authors: Joosten, Simone A., Smit van Dixhoorn, Mieneke G. A., Borrias, Maria C., Ham, Vanessa, Groot Koerkamp, Marian J. A., Savolainen‐Peltonen, Hanna M., Häyry, Pekka, Daha, Mohamed R., Kooten, Cees, Paul, Leendert C.
Format: Article
Language:English
Subjects:
Animals
Aorta - metabolism
Aorta - transplantation
Arteriosclerosis - etiology
Biological and medical sciences
Cyclin D1 - analysis
estrogen receptor
gene array
Gene Expression Profiling
General aspects
Immunohistochemistry
Male
Medical sciences
Nephrology. Urinary tract diseases
Pharmacology. Drug treatments
Polymerase Chain Reaction
Protein Precursors - analysis
Protein Precursors - genetics
prothymosin alpha
rat aorta transplantation
Rats
Rats, Inbred WF
Thymosin - analogs & derivatives
Thymosin - analysis
Thymosin - genetics
transplant arteriosclerosis
Transplantation, Homologous
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Summary:Summary Transplant arteriosclerosis is the result of intima proliferation in large vessels upon organ transplantation. Obliteration of the vascular lumen will ultimately lead to ischemia and late graft failure. Gene array analysis was performed to identify factors involved in the pathogenesis of transplant arteriosclerosis. Aortic transplants from Dark Agouti to Wistar Furth rats were performed to identify potential target genes. Hierarchical clustering of genes specifically upregulated in allogeneic but not in syngeneic aortas revealed 19 genes. A gene that fulfilled these criteria is prothymosin alpha (PTMA), a regulator of estrogen receptor transcriptional activity. PTMA gene and protein expression levels were confirmed by PCR and immunohistochemistry. Estrogen receptor staining was increased in allogeneic aortas. Furthermore, cyclin D1 a downstream target of PTMA, was also up regulated in allogeneic aortas. In conclusion, PTMA was identified as potential candidate gene involved in transplant arteriosclerosis.
ISSN:0934-0874
1432-2277
DOI:10.1111/j.1432-2277.2005.00157.x