Microarray analysis of a reversible model and an irreversible model of anti-Thy-1 nephritis.
Microarray analysis of a reversible model and an irreversible model of anti-Thy-1 nephritis.
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DOI：
10.1038/sj.ki.5000191
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发表时间：
2006-03
影响因子：
19.6
通讯作者：
M. Tsuji;T. Monkawa;J. Yoshino;M. Asai;S. Fukuda;H. Kawachi;F. Shimizu;M. Hayashi;T. Saruta
中科院分区：
文献类型：
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作者：
M. Tsuji;T. Monkawa;J. Yoshino;M. Asai;S. Fukuda;H. Kawachi;F. Shimizu;M. Hayashi;T. Saruta
单次静脉注射抗Thy-1单抗(MAb)1-22-3可引起可逆性系膜增生性肾炎。然而，单抗1-22-3注射后，单侧肾切除导致进行性肾小球硬化和肾小管间质改变，其过程是不可逆转的。为了确定在肾脏损伤不可逆发展过程中发挥重要作用的基因，我们使用微阵列技术来识别这些模型之间的基因表达差异。分别于单侧肾切除(不可逆模型)或假手术(可逆模型)后1周静脉注射单抗1-22-3，分别于注射后4、7、14、42、56天处死大鼠。将肾信使RNA制备的互补DNA探针与含有4854个大鼠基因的寡核苷酸芯片杂交。微阵列鉴定了189个差异表达基因，在两个模型之间至少有两倍的表达水平差异，并将它们分为五个簇。其中一个簇由基因组成，这些基因的表达在不可逆模型中显著上调。该簇包括骨桥蛋白、肾脏损伤分子-1和胸腺素β10的编码基因。胸腺素β10的表达增加主要定位于纤维化间质中的巨噬细胞，在单侧输尿管梗阻模型中也观察到胸腺素β10的表达上调。微阵列分析提供了关于可逆和不可逆抗Thy-1肾炎模型疾病进展差异的分子机制的信息。胸腺素β10可能在肾脏疾病的进展中起重要作用。
A single intravenous injection of anti-Thy-1 monoclonal antibody (mAb) 1-22-3 is known to cause reversible mesangial proliferative glomerulonephritis. However, mAb 1-22-3 injection followed by unilateral nephrectomy leads to progressive glomerulosclerosis and tubulointerstitial change with an irreversible course. To identify genes that play an important role in the irreversible progression of renal injury, we used microarray technology to identify differences in gene expression between these models. Rats were intravenously injected with mAb 1-22-3 1 week after unilateral nephrectomy (irreversible model) or a sham operation (reversible model), and rats were killed on days 4, 7, 14, 42, and 56 after the injection. complementary DNA probes prepared from kidney messenger RNAs were hybridized with oligonucleotide microarrays containing 4854 rat genes. The microarray identified 189 differentially expressed genes, having at least a two-fold difference in expression level between the two models, and they were classified into five clusters. One of the clusters consisted of genes whose expression was markedly upregulated in the irreversible model. This cluster included the genes encoding osteopontin, kidney injury molecule-1, and thymosinβ10. Increased expression of thymosinβ10 was localized mainly in macrophages in the fibrotic interstitium, and upregulation of thymosinβ10 expression was also observed in a unilateral ureteral obstruction model. The microarray analysis yielded information on the molecular mechanisms responsible for the difference in disease progression between the reversible and irreversible model of anti-Thy-1 nephritis. Thymosinβ10 may play an important role in the progression of kidney disease.