BACKGROUND: There is evidence that brain death causes changes in peripheral organs. Marked inflammation is found in organs collected during experimental brain death and clinical studies indicate that, despite genetic mismatch, organs obtained from living donors show improved survival over those from brain-dead donors. The aim of the present clinical research was to explore changes in the transcriptional profile of livers from brain-dead organ donors. METHODS: Using the cDNA macroarray technique, we compared gene expression in liver biopsies from 21 brain-dead organ donors and in normal liver tissue obtained during resection of benign focal lesions. RESULTS: Analysis of gene expression showed significant differences in the mRNA levels of 117 genes. There was reduced expression of 93 genes whereas expression of 24 genes was enhanced. Downregulated pathways included transcripts related to morphogenesis, blood coagulation, complement cascade, amine metabolism, lipid metabolism, nucleic acid metabolism, biodegradation of xenobiotics, signal transduction, and transcription. Conversely, there was induction of genes related to acute phase response, damage-related response, electron transport, and energy metabolism. CONCLUSIONS: The present research demonstrates major changes in the transcriptional profile of livers from brain-dead organ donors. The presence of both down- and upregulated gene families suggests that the alteration in transcriptional profile is not a consequence of death-associated organ failure, but rather, an active change in regulatory mechanisms.
Alteration in the trascriptional profile of livers from brain-dead organ donors
BONINO, FERRUCCIO;
2006-01-01
Abstract
BACKGROUND: There is evidence that brain death causes changes in peripheral organs. Marked inflammation is found in organs collected during experimental brain death and clinical studies indicate that, despite genetic mismatch, organs obtained from living donors show improved survival over those from brain-dead donors. The aim of the present clinical research was to explore changes in the transcriptional profile of livers from brain-dead organ donors. METHODS: Using the cDNA macroarray technique, we compared gene expression in liver biopsies from 21 brain-dead organ donors and in normal liver tissue obtained during resection of benign focal lesions. RESULTS: Analysis of gene expression showed significant differences in the mRNA levels of 117 genes. There was reduced expression of 93 genes whereas expression of 24 genes was enhanced. Downregulated pathways included transcripts related to morphogenesis, blood coagulation, complement cascade, amine metabolism, lipid metabolism, nucleic acid metabolism, biodegradation of xenobiotics, signal transduction, and transcription. Conversely, there was induction of genes related to acute phase response, damage-related response, electron transport, and energy metabolism. CONCLUSIONS: The present research demonstrates major changes in the transcriptional profile of livers from brain-dead organ donors. The presence of both down- and upregulated gene families suggests that the alteration in transcriptional profile is not a consequence of death-associated organ failure, but rather, an active change in regulatory mechanisms.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
