Department of Nephrology, Odense University Hospital, J. B. Winsløws Vej 4, 5000, Odense, Denmark.
Cardiovascular and Renal Research, Department of Molecular Medicine, University of Southern Denmark, J.B. Winsløws Vej 21.3, 5000, Odense C, Denmark.
Sci Rep. 2024 May 27;14(1):12112. doi: 10.1038/s41598-024-62149-1.
The forkhead box P3 (FOXP3) transcript is essential for tolerance of alloantigens. Here, we describe the expression of FOXP3 mRNA variants in healthy females and males, and in kidney transplant recipients (KTR). We measured FOXP3 in peripheral blood mononuclear cells from healthy kidney donors (N = 101), and in blood from KTRs (N = 248) before and after transplantation. FOXP3 was measured with quantitative polymerase chain reaction, and differentiated between pre-mature mRNA FOXP3, Total mature FOXP3, FOXP3 in which exon two is spliced, and full length FOXP3. We found similar levels of FOXP3 in healthy female and male kidney donors. We confirmed this result in a publicly available cohort (N = 33) of healthy individuals (GSE97475). Homogenously, female and male KTR FOXP3 levels were similar pre-transplantation, one day post-transplantation and 29 days post-transplantation. This may suggest that kidney transplantation and related immunosuppressive treatments do not influence FOXP3 expression differently in females and males. Finally, fold difference analysis revealed that KTRs express lower levels of mature FOXP3 and higher levels of pre-mature FOXP3 mRNA pre-transplant compared to healthy individuals. This finding may suggest higher pre-mRNA synthesis, lower pre-mRNA degradation, lower spliceosome efficiency or higher degradation of mature FOXP3 mRNA in kidney transplant candidates.
叉头框蛋白 P3(FOXP3)转录本对于同种异体抗原的耐受性至关重要。在这里,我们描述了 FOXP3 mRNA 变体在健康女性和男性以及肾移植受者(KTR)中的表达。我们测量了健康供肾者(N=101)和肾移植受者(N=248)外周血单个核细胞中的 FOXP3,包括移植前和移植后。使用定量聚合酶链反应(PCR)测量 FOXP3,并区分前体 mRNA FOXP3、总成熟 FOXP3、外显子 2 拼接的 FOXP3 和全长 FOXP3。我们发现健康女性和男性供肾者的 FOXP3 水平相似。我们在一个公开的健康个体队列(N=33)中证实了这一结果(GSE97475)。女性和男性 KTR 的 FOXP3 水平在移植前、移植后 1 天和移植后 29 天相似。这可能表明,肾移植和相关的免疫抑制治疗不会以不同的方式影响女性和男性的 FOXP3 表达。最后,折叠差异分析显示,与健康个体相比,肾移植受者在移植前表达的成熟 FOXP3 水平较低,前体 mRNA FOXP3 水平较高。这一发现可能表明,肾移植候选者中前体 mRNA 的合成更高,前体 mRNA 的降解更低,剪接体效率更低,或成熟 FOXP3 mRNA 的降解更高。
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