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Targeting Sirtuin-1 prolongs murine renal allograft survival and function
| Content Provider | Scilit |
|---|---|
| Author | Levine, Matthew H. Wang, Zhonglin Xiao, Haiyan Jiao, Jing Wang, Liqing Bhatti, Tricia R. Hancock, Wayne W. Beier, Ulf H. |
| Copyright Year | 2016 |
| Description | Journal: Kidney International Current immunosuppressive medications used after transplantation have significant toxicities. $Foxp3^{+}$ T-regulatory cells can prevent allograft rejection without compromising protective host immunity. Interestingly, inhibiting the class III histone/protein deacetylase Sirtuin-1 can augment $Foxp3^{+}$ T-regulatory suppressive function through increasing Foxp3 acetylation. Here we determined whether Sirtuin-1 targeting can stabilize biological allograft function. BALB/c kidney allografts were transplanted into C57BL/6 recipients with a CD4-conditional deletion of Sirtuin-1 $(Sirt1^{fl/fl}CD4^{cre}$) or mice treated with a Sirtuin-1–specific inhibitor (EX-527), and the native kidneys removed. Blood chemistries and hematocrit were followed weekly. $Sirt1^{fl/fl}CD4^{cre}$ recipients showed markedly longer survival and improved kidney function. $Sirt1^{fl/fl}CD4^{cre}$ recipients exhibited donor-specific tolerance, accepted BALB/c, but rejected third-party C3H cardiac allografts. C57BL/6 recipients of BALB/c renal allografts that were treated with EX-527 showed improved survival and renal function at 1, but not 10 mg/kg/day. Pharmacologic inhibition of Sirtuin-1 also improved renal allograft survival and function with dosing effects having relevance to outcome. Thus, inhibiting Sirtuin-1 can be a useful asset in controlling T-cell–mediated rejection. However, effects on non–T cells that could adversely affect allograft survival and function merit consideration. |
| Related Links | http://europepmc.org/articles/pmc4834143?pdf=render https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834143/pdf http://www.kidney-international.org/article/S0085253816003008/pdf |
| Ending Page | 1026 |
| Page Count | 11 |
| Starting Page | 1016 |
| ISSN | 00852538 |
| e-ISSN | 15231755 |
| DOI | 10.1016/j.kint.2015.12.051 |
| Journal | Kidney International |
| Issue Number | 5 |
| Volume Number | 89 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2016-03-16 |
| Access Restriction | Open |
| Subject Keyword | Journal: Kidney International Urology and Nephrology Acute Rejection Chronic Allograft Nephropathy |
| Content Type | Text |
| Resource Type | Article |
| Subject | Nephrology |
