Date: Tuesday, June 4, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Ischemia reperfusion (I/R) injury is a major contributor to short-term graft function. Dissecting organ specific and common molecular pathways associated with I/R injury among different organ types will provide further insight for targeting specific therapeutic interventions.
*Methods: A total of 222 gene expression (Affymetrix HG-U133Av2 Gene Chips) arrays were performed on allograft biopsies obtained from deceased donor kidney transplant recipients (n = 75) and liver transplant recipients (LTRs) (n = 36). From each patient, paired pre-implantation (PI) and post-reperfusion (PR) biopsies were obtained. Gene expression analysis was done using expression and transcriptome console softwares. PI and PR gene expression was compared in liver and kidney biopsies separately and probe sets were considered significant when the false discovery rate (FDR) was < 5 % and fold change greater than 1.5. IPA software and other gene enrichment and cell type enrichment softwares were used for further analysis of the data.
*Results: Comparing gene expression in PI and PR biopsies from LTRs resulted in 438 differentially expressed probe sets and similar analysis in KTRs yielded 366 differentially expressed probe sets. Upon comparing the early I/R response in liver and kidney, it was observed that 40 – 50 % of the differentially expressed genes were similar in both organs, with major pathways associated with inflammation and transcription regulation. Around 28% of the common genes were transcription factors. Furthermore, 12% were cytokines and growth factors ( IL6 signaling pathway, NF-KB signaling, HMGB1 signaling, and production of NO and ROS in macrophages). In the other hand, unique genes associated with liver specific I/R response, involved growth factors and cytokines that relate to wound healing and additional reparative processes like angiogenesis. Additional molecular pathways involved in functions like T cell development, lymphopoiesis and response of neutrophils were exacerbated in the liver tissues. Otherwise, in kidney I/R the initial unique molecular pathways were those involved in inhibition of growth of connective tissue
*Conclusions: Common intra-allograft inflammatory responses to I/R injury between kidney and liver transplantation were identified. However, liver grafts presented a faster activation of molecular profiles associated with regenerative, reparative and growth factors related functions
To cite this abstract in AMA style:Bontha S, Bajwa A, Gallon L, Eason J, Maluf D, Mas V. Organ-Specific Injury and Recovery Mechanisms in Post-Transplant Ischemia Reperfusion Injury [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/organ-specific-injury-and-recovery-mechanisms-in-post-transplant-ischemia-reperfusion-injury/. Accessed September 19, 2020.
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