Expressions of Angiopoietin-1, Angiopoietin-2, and Tie2 and Their Roles in Rat Renal Allografts With Chronic Allograft Nephropathy
Expressions of Angiopoietin-1, Angiopoietin-2, and Tie2 and Their Roles in Rat Renal Allografts With Chronic Allograft Nephropathy
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DOI：
10.1016/j.transproceed.2008.07.121
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发表时间：
2008-10-01
影响因子：
0.9
通讯作者：
Li, Y. P.
中科院分区：
文献类型：
--
作者：
Ma, X.;Lu, Y. P.;Li, Y. P.
Objective.血管生成素-1（Ang 1）和-2（Ang 2）是内皮特异性酪氨酸激酶Tie 2的2个配体。既往研究表明，Ang 1、Ang 2和Tie 2的相互调节在慢性移植心脏血管病变中起重要作用。本研究探讨了Ang 1，Ang 2和Tie 2在慢性移植肾肾病（CAN）大鼠移植肾中的表达。采用Fisher（F344，RTIlv 1）大鼠作为供体和受体，在自体肾移植组中原位进行Kamada改良肾移植术。同种异体移植组以Fisher和刘易斯（LEW，RTI 1）大鼠为供、受体，给予环孢素A（CsA; 10 mg/kg/d × 10 d）治疗。分别于术后4周、8周和12周检测血清肌酐（SCr），并按Banff 97标准评价病理改变。采用实时荧光定量聚合酶链反应（PCR）和免疫组织化学方法对Ang 1、Ang 2和Tie 2的mRNA（Delta ct）和蛋白表达进行定位。术后8周和12周，所有移植物均出现SCr升高和CAN病理改变。Ang 1和Ang 2的表达定位于肾小球的上皮细胞和血管束的内皮细胞; Tie 2在移植后的所有时间点特异性表达于自体和同种异体移植物的血管内皮细胞。4周时，两组间Ang 1、Ang 2和Tie 2的mRNA表达差异无统计学意义（P > 0.05）。与自体移植物相比，Ang 1的mRNA表达显著降低（8周和12周分别为P =.008和.003），Ang 2和Tie 2的nnRNA表达显著增加（8周和12周分别为P =.001/.006和.005/.001）。3个基因的表达变化与移植物的Banff评分相关。提示Ang 1、Ang 2和Tie 2的异常表达及其相互调节可能在大鼠移植肾CAN的发生发展中起重要作用。
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, RTIlv1) rats as both donors and recipients in the autograft group. Fisher and Lewis (LEW, RTI1) 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 (Delta ct) 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 nnRNA 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.