Genetic profiling of aortic allografts: prothymosin alpha as potential target?
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.
Joosten
Simone A
SA
Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
Smit van Dixhoorn
Mieneke G A
MG
Borrias
Maria C
MC
Ham
Vanessa
V
Groot Koerkamp
Marian J A
MJ
Savolainen-Peltonen
Hanna M
HM
Häyry
Pekka
P
Daha
Mohamed R
MR
Kooten
Cees
C
Paul
Leendert C
LC
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000637:transplantation*; D001161:Arteriosclerosis / Q000209:etiology*; D019938:Cyclin D1 / Q000032:analysis; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D008297:Male; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000032:analysis / Q000235:genetics*; D051381:Rats; D011920:Rats, Inbred WF; D013947:Thymosin / Q000031:analogs & derivatives* / Q000032:analysis / Q000235:genetics; D014184:Transplantation, Homologous
D011498:Protein Precursors; C040782:prothymosin alpha; D019938:Cyclin D1; D013947:Thymosin