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.
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.