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首页> 外文期刊>Transplantation Proceedings >Expressions of Angiopoietin-1, Angiopoietin-2, and Tie2 and their roles in rat renal allografts with chronic allograft nephropathy.
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Expressions of Angiopoietin-1, Angiopoietin-2, and Tie2 and their roles in rat renal allografts with chronic allograft nephropathy.

机译:血管生成素-1,血管生成素-2和Tie2的表达及其在大鼠慢性同种异体肾病肾移植物中的作用。

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OBJECTIVE: Angiopoietin-1 (Ang1) and -2(Ang2) are 2 ligands for the endothelium-specific tyrosine kinase Tie2. Previous studies have shown that reciprocal regulation of Ang1, Ang2, and Tie2 plays an important role in chronic cardiac allograft vasculopathy. This study investigated the expressions of Ang1, Ang2, and Tie2 in rat renal allografts undergoing chronic allograft nephropathy (CAN). MATERIALS AND METHODS: Renal transplantations following the procedure of Kamada with our modification were orthotopically performed using Fisher (F344, RT1(1v1)) rats as both donors and recipients in the autograft group. Fisher and Lewis (LEW, RT1(1)) rats were used as donors and recipients in the allograft group, respectively, which was treated with cyclosporine (CsA; 10 mg/kg/d x 10 d). At 4w, 8w, and 12 weeks posttransplantation, serum creatinine (SCr) was measured and pathologic changes assessed according to the Banff 97 criteria. The mRNA (Deltact) and protein expressions of Ang1, Ang2, and Tie2 were localized by real-time fluorescence quantitative polymerase chain reaction (PCR) and by immunohistochemistry. RESULTS: The elevation in SCr and the pathologic changes in CAN were observed in all allografts at 8 and 12 weeks. The expressions of Ang1 and Ang2 were localized to epithelial cells and endothelium of the vascular bundles of the glomeruli; Tie2 was specifically expressed in endothelium of vessels both in auto- and allografts at all time points posttransplantation. At 4 weeks, the differences in mRNA expression of Ang1, Ang2, and Tie2 between the 2 groups were not significant (P > .05). Compared with autografts, the mRNA expression of Ang1 decreased significantly (P = .008 and .003 for 8 and 12 weeks, respectively), and the mRNA expressions of Ang2 and Tie2 significantly increased (P = .001/.006 and .005/.001 for 8 and 12 weeks, respectively). The changes in expression of all 3 genes showed significant correlation with the Banff score in the allografts. CONCLUSION: This study suggested that the abnormal expression and reciprocal regulation of Ang1, Ang2, and Tie2 may play important roles in the development of CAN in rat renal allografts.
机译:目的:Angiopoietin-1(Ang1)和-2(Ang2)是内皮特异性酪氨酸激酶Tie2的2个配体。先前的研究表明,Ang1,Ang2和Tie2的相互调节在慢性同种异体移植血管病中起重要作用。这项研究调查了Ang1,Ang2和Tie2在经历慢性同种异体肾病(CAN)的大鼠肾同种异体移植物中的表达。材料与方法:采用Kamada改良程序进行肾脏移植,原位移植使用Fisher(F344,RT1(1v1))大鼠作为自体移植组的供体和受体。 Fisher和Lewis(LEW,RT1(1))大鼠分别用作同种异体移植组的供体和受体,并用环孢素(CsA; 10 mg / kg / d x 10 d)处理。移植后4周,8周和12周时,根据Banff 97标准测量血清肌酐(SCr)并评估病理变化。实时荧光定量聚合酶链反应(PCR)和免疫组织化学法定位Ang1,Ang2和Tie2的mRNA(Deltact)和蛋白质表达。结果:在第8周和第12周,所有同种异体移植物中均观察到SCr的升高和CAN的病理变化。 Ang1和Ang2的表达局限于肾小球血管束的上皮细胞和内皮。在移植后的所有时间点,Tie2在自体和同种异体移植的血管内皮中均特异性表达。在第4周,两组之间Ang1,Ang2和Tie2的mRNA表达差异无统计学意义(P> 0.05)。与自体移植相比,Ang1的mRNA表达显着降低(分别为8和12周的P = 0.008和.003),而Ang2和Tie2的mRNA表达则显着升高(P = 0.001 / .006和.005 / .001,分别为8周和12周)。在同种异体移植物中,所有3种基因的表达变化均与Banff评分显着相关。结论:本研究提示Ang1,Ang2和Tie2的异常表达和相互调节可能在大鼠肾同种异体移植CAN的发生中起重要作用。

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