Date: Saturday, June 1, 2019
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall C & D
*Purpose: We previously showed that CD137 ligand (CD137L) reverse signaling play a central role in kidney ischemia-reperfusion injury (IRI) by amplifying acute renal injury. In this study, we explored whether CD137L signaling is involved in the tissue repair process during kidney IRI.
*Methods: Kidney ischemia-reperfusion injury was induced in C57BL/6 mice and 50 ug of CD137-Fc fusion protein per mouse was injected at day 1 after kidney IRI. The extent of renal injury, renal inflammation and tissue repair was analyzed using qRT-PCR and flow cytometry. Bone marrow-derived macrophages were stimulated with a copmbination of CD137-Fc abd GM-CSF and whole RNA sequencing was performed 24 hours after stimulation.
*Results: Firstly, injection of CD137-Fc fusion protein at day 1 after kidney IRI decreased renal inflammation and injury. These phenomena were associated with recruitment of a lower number of neutrophils and increase in the ratio of M2 macrophage-to-M1 macrophage. Secondly, administration of CD137-Fc enhanced expression of tissue repair genes, PDGFα, IL-22, Amphiregulin, IGF1, and TGF-β. Thirdly, there was a higher proliferation of tubular epithelial cells in CD137-Fc-injected mouse kidneys, concomitantly with increased expression of Vementin. Finally, ten days after kidney IRI, renal inflammation was almost completely resolved and renal macrophages showed a normal phenotype in CD137-Fc-injected mice. RNA seq data showed that CD137L signaling induced functionally different macrophages from naïve macrophages and GM-CSF and CD137L signaling synergistically increased expression of some anti-inflammatory and tissue-repair genes.
*Conclusions: In sum, our results indicate that CD137L signaling is indispensable for tissue repair following kidney IRI. Therefore, our findings have important clinical implications in kidney regeneration.
To cite this abstract in AMA style:Cho HR, Lee S, Lee JS, Park SJ, Kwon B. Reverse Signaling through CD137 Ligand Promotes Tissue Repair after Ischemia-Reperfusion Kidney Injury [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/reverse-signaling-through-cd137-ligand-promotes-tissue-repair-after-ischemia-reperfusion-kidney-injury/. Accessed May 9, 2021.
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