Urinary transforming growth factor-β-induced gene-h3 (βig-h3) as a sensitive predictor in chronic cyclosporine nepfirotoxicity
Urinary transforming growth factor-β-induced gene-h3 (βig-h3) as a sensitive predictor in chronic cyclosporine nepfirotoxicity
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DOI：
10.1016/j.transproceed.2006.02.070
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发表时间：
2006-06-01
影响因子：
0.9
通讯作者：
Kim, Y. L.
中科院分区：
文献类型：
--
作者：
Kim, C. -D.;Cho, Y. -J.;Kim, Y. L.
转化生长因子（TGF）-β参与慢性环孢素肾毒性（CyAN）的发病机制。由于TGF-β诱导的基因h3（β ig-h3）的表达受TGF-β上调，我们评估了β IG-0作为监测慢性CyAN进展/消退的敏感尿标志物的潜在作用。尿β ig-h3水平测定使用酶联免疫吸附试验在9例慢性CyAN和13例稳定移植功能的患者。我们对慢性CyAN患者肾小管间质纤维化（TIF）的程度进行评分，并使用免疫过氧化物酶标记法测定肾组织中β ig-h3的表达。慢性CyAN患者的尿β ig-h3排泄量高于对照组（173.4 +/- 26.0 vs 62.6 +/- 5.0 ng/mg肌酐，P <0.01）。在慢性CyAN中，TIF的程度与尿β ig-h3水平升高相关（r = 0.785，P <0.05）。在慢性CyAN肾脏中，β ig-h3标记在肾小管基底膜（13 M）处更为突出，其中炎性细胞已浸润周围肾小管。此外，萎缩小管的BM及其周围的肾小管被强烈标记。尿β ig-h3水平从173.4 +/- 26.0下降到64.9 +/- 14.4 ng/mg肌酐，在停用CYA或减少CyA剂量后1个月（P <0.01），尽管血清肌酐水平不变。尿β ig-h3水平在慢性CyAN患者中升高，在停用或减少CyA剂量后降低。提示尿β ig-h3水平可作为监测慢性CyAN进展或消退的敏感指标。
Transforming growth factor (TGF)-beta is involved in the pathogenesis of chronic cyclosporine nephrotoxicity (CyAN). Since the expression of TGF-beta induced gene h3 (beta ig-h3) is up-regulated by TGF-beta, we evaluated the potential role of beta ig-0 as a sensitive urinary marker to monitor the progression/regression of chronic CyAN. Urinary beta ig-h3 levels were determined using an enzyme-linked immunosorbent assay in nine patients with chronic CyAN and 13 patients with stable graft function. We scored the extent of tubulointerstitial fibrosis (TIF) and using immunoperoxidase labeling, determined beta ig-h3 expression in renal tissues of patients with chronic CyAN. Urinary beta ig-h3 excretion was higher in chronic CyAN compared to control subjects (173.4 +/- 26.0 vs 62.6 +/- 5.0 ng/mg creatinine, P < .01). In chronic CyAN, the degree of TIF correlated with increased urinary beta ig-h3 levels (r = .785, P < .05). In kidneys with chronic CyAN, beta ig-h3 labeling was more prominent at the basement membranes (13M) of the tubules where inflammatory cells had infiltrated the surrounding interstitium. Moreover, the BM of the atrophied tubules and their surrounding interstitium were strongly labeled. Urinary beta ig-h3 levels decreased from 173.4 +/- 26.0 to 64.9 +/- 14.4 ng/mg creatinine at 1 month after discontinuation of CYA or reduction in CyA dosage (P < .01) despite unchanged serum creatinine levels. Urinary beta ig-h3 levels increased in patients with chronic CyAN and decreased after discontinuation or reduction of CyA dosage. Our results suggested that urinary beta ig-h3 levels could be used as a sensitive urinary marker to monitor the progression or regression of chronic CyAN.