EXPRESSION OF 2 IMMEDIATE EARLY GENES, EGR-1 AND C-FOS, IN RESPONSE TO RENAL ISCHEMIA AND DURING COMPENSATORY RENAL HYPERTROPHY IN MICE

EXPRESSION OF 2 IMMEDIATE EARLY GENES, EGR-1 AND C-FOS, IN RESPONSE TO RENAL ISCHEMIA AND DURING COMPENSATORY RENAL HYPERTROPHY IN MICE
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DOI:
10.1172/jci114502
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发表时间:
1990-03-01
影响因子:
15.9
通讯作者:
BONVENTRE, JV
BONVENTRE, JV
中科院分区:
医学1区
文献类型:
--
作者:
OUELLETTE, AJ;MALT, RA;BONVENTRE, JV

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为了确定与肾缺血相关的特定遗传调控机制,我们测量了肾动脉闭塞和再灌注后小鼠肾脏中Egr-1和c-fos mRNA的积累。在右肾切除术和对侧肾动脉闭塞10或30分钟后1小时,Egr-1 mRNA水平在这些肾脏中的3至5倍,与对照组动物相比,持续单侧肾切除术,并远远高于正常器官中的水平。无论是缺血10或30分钟,肾Egr-1 mRNA的含量是相等的,并保持升高后24小时再灌注30分钟的缺血。虽然c-fos mRNA也积累在响应缺血和再灌注,模式不同,Egr-1的c-fos mRNA含量随缺血时间的变化,并在损伤后24小时检测不到。单侧肾缺血时Egr-1和c-fos mRNA的明显积聚不需要行单侧肾切除。然而,由于在缺血期结束时仅发生最小序列累积,因此必须进行再流。左单侧肾切除术后,Egr-I mRNA水平在手术后30分钟最高,但此后检测不到; c-fos mRNA水平在单侧肾切除术后没有变化。早期生长相关基因转录激活的差异表达可能影响组织恢复肾缺血。
To identify specific genetic regulatory mechanisms associated with renal ischemia, we measured the accumulation of Egr-1 and c-fos mRNAs in the mouse kidney after occlusion of the renal artery and reperfusion. At 1 h after right nephrectomy and arterial occlusion of the contralateral kidney for 10 or 30 min, Egr-1 mRNA levels were three to five times greater in these kidneys as compared with those in control animals that had sustained unilateral nephrectomy alone and were much greater than levels in the normal organ. Whether ischemia was imposed for 10 or for 30 min, renal Egr-1 mRNA contents were equivalent and remained elevated after 24 h of reperfusion subsequent to 30 min of ischemia. Although c-fos mRNA also accumulated in response to ischemia and reperfusion, the pattern differed from that of Egr-1 in that c-fos mRNA content varied with the duration of ischemia and was undetectable 24 h after injury. Contralateral nephrectomy was not necessary to see the marked accumulation of Egr-1 and c-fos mRNAs with unilateral ischemia. Reflow was necessary, however, since only minimal sequence accumulation occurred by the end of the ischemic period. After left uninephrectomy alone, Egr-I mRNA levels in the remaining kidney were maximal 30 min after surgery, but were not detectable thereafter; c-fos mRNA levels did not change after unilateral nephrectomy. Differential expression of early growth-related genes implicated in transcriptional activation may influence tissue recovery renal ischemia.