Background: Ischemia-reperfusion injury (IRI) in kidney transplantation is associated with delayed graft function and chronic allograft injury. microRNA (miRNA) are part of a population of non-coding RNAs (NCR) derivative of the non-protein-coding portion of the genome. NCR are important in normal physiology and disease, including IRI. Thus, miRNA including miR-21 and eight other miRNA are altered in IRI of the kidney early in the reperfusion period (PNAS,107:14339), however it is unclear if changes in the miRNA trasnscriptome are time dependent. In clinical kidney transplantation, examination of the gene expression signature later in the reperfusion period may be of use in defining 1) the status of molecular disarray at the time of wound closure and/or 2) signaling systems that may facilitate development of delayed graft function or chronic allograft injury. To test this question we assessed the miRNA transcriptome from rats exposed to IRI following a 60 min recovery period.

Methods: Male SD rats (N=5/group) underwent IRI (30 min ischemia, 60 min recovery) or sham surgery. At sacrifice one kidney from each animal was snap frozen and the renal cortical transcriptome hybridized to the GeneChip®Rat Gene 1.0 ST Array (Affymetrix).

Results: Of the 8711 probe sets represented on the chip, 87 were miRNA. Limma was used to test for differential gene expression. IRI resulted in significant change in 914 (10.5%) of all transcripts. Eight miRNA were significantly changed by IRI (FDR adjusted p-value): miR-196b (0.014), miR-32 (0.018), miR-29b-2 (0.019), miR-29c (0.025), miR-30e (0.030), miR-29a (0.033), miR-207 (0.040) and miR-188 (0.049). The early activation miRNA, mi-R21, had a p value of 0.088, suggesting its activation was fading by 60 minutes. These data indicate that after 60 minutes of reperfusion a unique set of miRNA emerge as being significantly altered.

Conclusions: Renal IRI with 60 minutes of reperfusion induces changes in a unique set of miRNA from those in the immediate reperfusion period. Defining the regulatory role of these transcripts may give clues to the activation of pathologic pathways triggered by IRI in clinical transplantation.

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