Franny Jongbloed

211 8 BENEFICIAL EFFECTS OF A PREOPERATIVE DIET (A) Female donors (B) Male donors = CCPR = Control Figure 4. Principal component analysis of kidney tissue in female and male donors. (A) The unbiased principal component analysis (PCA) of all female donors showed the most variation of genes on the principal component (PC) axis 1 and some clustering of the two intervention groups is shown. (B) The PCA of the male donors was based on only three kidneys in the CCPR group, and showed little variation on PC axis 2. Principal component (PC) 1 is depicted on the x-axis and PC2 is depicted on the y-axis, followed by the percentage of variance explained by each axis. Each symbol represents one sample of one donor. Samples of the same group are shown in the same color. CCPR = combined calorie and protein restriction. The CCPR group of female donors showed 480 differentially expressed transcripts (DET), of which 239 were downregulated and 241 upregulated. Pathway analysis showed a trend towards downregulation of pathways as shown by the more pronounced presence of downregulated genes in these pathways. However, the inhibitory directionality of these pathways was not statistically significant as evidenced by the absence of a z-score. One pathway was significantly upregulated with a z-score >2, namely EIF2 Signaling (Table 4A). Other, not significantly activated pathways included the NRF2-mediated Oxidative Stress Response , cell cycle regulator Cell Cycle: G2/M DNA Damage Checkpoint Regulation and amino acid metabolism. Analysis of upstream transcription factors (TFs) in female donors revealed three significantly activated TFs, namely MYCN, MYC and NKX2-3. In addition, two TFs were significantly inhibited, namely PRDM1 and SMARCB1 (Table 3B).