Expression of protective genes in human renal allografts: a regulatory response to injury associated with graft rejection1,2

Abstract

This data demonstrate that A20 and HO-1 are up-regulated in response to immune injury inferred by AR. Given the antiapoptotic and antiinflammatory functions of these genes, we hypothesize that their expression survives to limit graft injury by maintaining cell viability and controlling inflammation. Their reduced expression in CR as compared with AR represents either inadequate response to injury or a sequelae of prior injury that jeopardizes further tissue response to immune attack.

Differential Expression of Heme Oxygenase-1 and Vascular Endothelial Growth Factor in Cadaveric and Living Donor Kidneys after Ischemia-Reperfusion

“…Although the glomerular expression of VEGF has been previously described in normal human kidneys (27), conflicting findings have been reported regarding the glomerular production of HO-1, being detected in transplanted patients with acute rejection (28) but not in patients with glomerulopathies (29). In our series, HO-1 and VEGF staining were less intense in some kidney biopsies from cadaveric donors, suggesting that the protein expression may also be altered in cadaveric donor kidneys during ischemia-reperfusion.…”

Association of Functional Heme Oxygenase-1 Gene Promoter Polymorphism with Renal Transplantation Outcomes

“…It is likely that there are other protective gene variants or molecules in renal transplantation (20), and that redundancy within this milieu allows compensation for a genetic predisposition towards lower HO-1 production. Thus, the HO-1 genotype may alter the cellular response to injury but this is masked clinically.…”

On the Intraoperative Molecular Status of Renal Allografts after Vascular Reperfusion and Clinical Outcomes

“…Total RNA was isolated from tissue homogenate samples with a commercial kit (RNeasy kit; Qiagen Inc, Chatworth, CA) (17). Reverse transcription of 1 mg of RNA was performed using multiscribed reverse transcriptase enzyme (PE Applied Biosystems, CA).…”

“…We have tested the hypothesis that molecular evidence of intragraft inflammation and active T cell immunity present intraoperatively at the zero-hour and detected via PCRbased transcriptional profiling are linked to adverse posttransplant clinical outcomes such as DGF, AR within 3 mo following transplantation, and the quality of graft function 6 mo posttransplantation. A predictive role for suboptimal expression of anti-apoptotic genes, some expressed in response to inflammation (hemoxygenase-1 and A20) (12)(13)(14)(15)(16)(17) and others not triggered by inflammation, was also investigated. In short, identification of pertinent molecular markers at the zero-hour provides a keen insight into future clinical outcomes.…”