Living kidney donors and hypoxia-inducible factor-1alpha.
BACKGROUND
Hypoxia inducible factor (HIF)-1, a heterodimeric transcription factor composed of alpha and beta subunits, is induced in the adaptive response to hypoxia and is critical for initiating the transcriptional activation of growth factors. We speculate that prolonged ischemia and hypoxia time leads to the production of HIF-1alpha, which in turn induces the production of fibrogenic cytokines in the graft.


METHODS
To investigate our hypothesis, we measured the expression of HIF-1alpha in time-zero biopsy specimens from living-donor kidneys (< or =2.5 hr of ischemia) and cadaveric donor kidneys (12-32 hr of ischemia).


RESULTS
By real time reverse-transcriptase polymerase chain reaction analysis, the mRNA expression level of HIF-1alpha was fivefold lower in time-zero biopsy specimens from living-donor kidneys than in specimens from cadaveric donor kidneys. In these time-zero biopsy specimens, the mRNA expression level of the fibrogenic cytokine transforming growth factor-beta was also significantly lower (twofold).


CONCLUSIONS
Low HIF-1alpha mRNA expression levels correlate with short ischemia times and prevent the transcription of fibrogenic cytokines that initiate the irreversible process of graft fibrosis.
Baan
Carla
C
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. baan@inw1.azr.nl
van Gelder
Teun
T
Peeters
Annemiek
A
Mol
Wendy
W
Niesters
Hubert
H
Weimar
Willem
W
IJzermans
Jan
J
D001706:Biopsy; D005355:Fibrosis; D015870:Gene Expression / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007668:Kidney / Q000473:pathology / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D012333:RNA, Messenger / Q000032:analysis; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology*
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D014157:Transcription Factors