Scientific contributionIschemia–reperfusion injury: KidneyUp-Regulation of Osteopontin, Chemokines, Adhesion Molecule, and Heat Shock Proteins in 1-Hour Biopsy From Cardiac Death Donor Kidneys
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Materials and Methods
All kidney grafts were procured at our center using an in situ regional cooling technique from DCD. Living donor kidneys (LD) were procured by open nephrectomy. All graft biopsies performed 1 hour after reperfusion were obtained from the renal cortex (DCD n = 8, LD n = 9). All biopsy specimens were immediately submerged in RNAlater (Ambion) for storage. Biopsy specimens were homogenized and total RNA purified using an RNeasy Mini kit (Qiagen, Valencia, Calif, USA). The expression profile of
Results
One hundred seventy eight genes were up-regulated (>2-fold difference and DCD/LD >1.5; P < .05) in DCD kidneys. Expression of osteopontin (22.5 ± 2.6–fold DCD vs 7.7 ± 1.7 LD; P < .001), chemokines (CCL4 4.4 ± 0.7 vs 2.5 ± 0.3; P < .01; CCL2 6.0 ± 1.3 vs 2.8 ± 0.5, CXCL1 9.5 ± 0.4 vs 2.0 ± 0.2, and CXCL2 16.7 ± 5.3 vs 4.8 ± 1.3; P < .05), adhesion molecules (ICAM-1 4.7 ± 0.7 vs 2.5 ± 0.4; P < .05), and heat shock proteins (HSPs; HSPA1L 6.7 ± 0.7 vs 1.6 ± 0.3, HSPA1A 17.7 ± 2.6 vs 2.4 ± 0.5,
Discussion
The present study showed that DCD caused increased expression of chemokines, adhesion molecules, and the stress-related HSPs in grafts. Osteopontin, a potent chemoattractant for mononuclear cells that is up-regulated in various inflammatory states of the kidney, was markedly up-regulated in DCD grafts. Expression of osteopontin is known to be induced in the tubular epithelium by ischemia-reperfusion injury and renal allograft rejection.3, 4 However, the mechanistic pathway of increased
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