Date: Tuesday, May 5, 2015
Session Name: Poster Session D: Innate Immunity in Transplantation
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Introduction: Histone/protein deacetylases (HDACs) regulate gene expression by modifying chromatin accessibility and protein acetylation. We have previously found that deletion of HDAC2 protects from renal ischemia-reperfusion injury (IRI) and wished both to determine the tissue specificity of the HDAC2 deletion on renal IRI tolerance and to evaluate its influence in a transplant model of cold ischemia.
Methods: We transplanted renal isografts from C57BL/6 (B6) mice with inducible HDAC2 gene deletion into wild type B6 mice (HDAC2KO->B6), from B6 into inducible HDAC2 deletion mice (B6->HDAC2KO), or B6 into B6 mice (B6->B6). To assess warm IRI tolerance, mice underwent native nephrectomy, tamoxifen-induced HDAC2 deletion, and standardized 25-minute warm IRI with clamping of the transplanted renal pedicle. To evaluate cold IRI tolerance, kidneys were procured from gene-deleted mice, stored on ice for 18 hours before implantation, and transplanted.
Results: HDAC2KO->B6 mice (n =10) demonstrated significant improvement in warm IRI tolerance with lower daily BUN levels over the 4 days following IRI compared to B6->HDAC2KO mice (n=5, p=0.0001) and B6->B6 mice (n=5, p=0.0003) (Figure 1) and significant reduction in renal fibrosis by Sirius Red staining at 28-days post-injury compared to both other groups (p=0.0128 and p=0.0136). HDAC2KO->B6 mice displayed significantly improved BUN (p=0.0187) and Cr (p=0.0012) compared to B6->B6 controls following renal transplant with 18 hours of cold ischemic time and had a trend towards improved survival (80% vs. 67%, p=0.43).
Conclusion: The profound effect of HDAC2 deletion on renal IRI is intrinsic to the kidney and extends to decreased renal injury post-cold ischemia and renal transplantation.
To cite this abstract in AMA style:Aufhauser D, Wang Z, Cheraghlou S, Bhatti T, Hancock W, Levine M. Profound Effect of HDAC2 Deletion on Renal Ischemia-Reperfusion Injury Is Intrinsic to the Kidney and Includes Protection Against Cold Ischemia [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/profound-effect-of-hdac2-deletion-on-renal-ischemia-reperfusion-injury-is-intrinsic-to-the-kidney-and-includes-protection-against-cold-ischemia/. Accessed January 25, 2021.
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