Identification of persistently altered gene expression in the kidney after functional recovery from ischemic acute renal failure
Identification of persistently altered gene expression in the kidney after functional recovery from ischemic acute renal failure
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DOI：
10.1152/ajprenal.00329.2004
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发表时间：
2005-05-01
影响因子：
4.2
通讯作者：
Cowley, AW
中科院分区：
文献类型：
--
作者：
Basile, DP;Fredrich, K;Cowley, AW
缺血性急性肾功能衰竭（ARF）的恢复涉及一个充分描述的再生过程;然而，ARF的恢复也会导致进行性肾脏疾病的易感性，这一点尚不清楚。本研究旨在确定肾基因表达的改变，在缺血后，恢复动物，可能发挥重要作用，这种进行性疾病。从假手术对照大鼠或双侧缺血再灌注（I/R）损伤恢复后35天的大鼠中分离的RNA使用含有类似于2,000个已知大鼠基因的cDNA微阵列进行比较。参考杂交策略用于定义99.9%的区间，并确定16个基因，持续改变后恢复I/R损伤（12个上调和4个下调）。实时PCR证实了已被阳性鉴定的8个基因中的6个基因的表达改变。确定的几个基因以前没有在ARF的背景下进行过评价。S100 A4是成纤维细胞的特异性标志物，在存在缺血后损伤的间质细胞群体中被鉴定。在缺血后的早期时间点，在肾小管细胞中也发现了S100 A4阳性细胞。与钙化相关的基因，包括骨桥蛋白和基质G1 a蛋白，也增强缺血后损伤。几个促炎基因被确定，包括补体C4，在缺血后组织中增强。相反，肾激肽释放酶表达在缺血后肾中特异性降低。总之，在ARF恢复后的大鼠肾脏中鉴定出具有已知炎症、重塑和血管活性的基因，其中一些基因可能在ARF恢复后改变长期肾功能中发挥作用。
Recovery from ischemic acute renal failure (ARF) involves a well-described regenerative process; however, recovery from ARF also results in a predisposition to a progressive renal disease that is not well understood. This study sought to identify alterations in renal gene expression in postischemic, recovered animals that might play important roles in this progressive disorder. RNA isolated from shamoperated control rats or rats 35 days after recovery from bilateral ischemia-reperfusion (I/R) injury was compared using a cDNA microarray containing similar to 2,000 known rat genes. A reference hybridization strategy was utilized to define a 99.9% interval and to identify 16 genes that were persistently altered after recovery from I/R injury (12 were upregulated and 4 were downregulated). Real-time PCR verified the altered expression of six of eight genes that had been positively identified. Several genes that were identified had not previously been evaluated within the context of ARF. S100A4, a specific marker of fibroblasts, was identified in a population of interstitial cells that were present postischemic injury. S100A4-positive cells were also identified in tubular cells at earlier time points postischemia. Genes associated with calcification, including osteopontin and matrix G1a protein, were also enhanced postischemic injury. Several proinflammatory genes were identified, including complement C4, were enhanced in postischemic tissues. Conversely, renal kallikrein expression was specifically reduced in the postischemic kidney. In summary, genes with known inflammatory, remodeling, and vasoactive activities were identified in rat kidneys after recovery from ARF, some of which may play a role in altering long-term renal function after recovery from ARF.