Abstract
Sirtuin 1, a member of sirtuin family of histone deacetylase enzymes, has been implicated in a variety of physiologic and pathologic events, including energy metabolism, cell survival, and age-related alterations. In view of the anti-inflammatory properties of sirtuin 1 along with its protective role in ischemia reperfusion injury, it might be considered as contributing to the promotion of transplantation outcome. However, the potential ability of sirtuin 1 to induce malignancies raises some concerns about its overexpression in clinic. Moreover, despite the findings of sirtuin 1 implication in thymic tolerance induction and T regulatory (Treg) cells survival, there is also evidence for its involvement in Treg suppression and in T helper 17 cells differentiation. The identification of sirtuin 1 natural and synthetic activators leads to the proposal of sirtuin 1 as an eligible target for clinical interventions in transplantation. All positive and negative consequences of sirtuin 1 overactivation/overexpression in the allograft should therefore be studied thoroughly. Herein, we summarize previous findings concerning direct and indirect influences of sirtuin 1 manipulation on transplantation.
Highlights
Transplantation is considered as one of the most significant improvements in treating end-stage organ failure
The availability of sirtuin 1 (Sirt1) activator and inhibitor agents [15] makes it an appealing target to investigate in transplantation; we review the advantages and disadvantages of Sirt1 overexpression/ overactivation in allograft tissue with the aim of providing an insight into its application as a supplementary substance to improve graft survival
It has been shown that Sirt1 plays a role in tissue maintenance and repair in the liver and kidney [63]
Summary
Transplantation is considered as one of the most significant improvements in treating end-stage organ failure. There have been some efforts to target certain molecules for specific inhibition of alloimmune responses [4]; in addition, various tolerance induction methods are studied in clinical trials [5]; a novel strategy may be envisaged by manipulating certain molecular pathways involved in tissue maintenance and hypoxia resistance [6]. For this purpose, sirtuin 1 (Sirt1) as a molecule with tissue protective potential might be a considerable candidate. The availability of Sirt activator and inhibitor agents [15] makes it an appealing target to investigate in transplantation; we review the advantages and disadvantages of Sirt overexpression/ overactivation in allograft tissue with the aim of providing an insight into its application (or not) as a supplementary substance to improve graft survival
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