Altered EGF expression and thyroxine metabolism in kidneys following acute ischemic injury in rat.
Altered EGF expression and thyroxine metabolism in kidneys following acute ischemic injury in rat.
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大鼠急性缺血性损伤后肾脏中 EGF 表达和甲状腺素代谢的改变。
DOI：
10.1152/ajprenal.1996.270.1.f21
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Hammerman,MR
中科院分区：
文献类型：
--
作者：
Rogers,SA;Miller,SB;Hammerman,MR
为了明确急性肾功能衰竭时肾脏表皮生长因子(EGF)表达与甲状腺激素的关系，我们对大鼠急性缺血性肾损伤后肾脏甲状腺激素-EGF轴进行了分析。伤后24 h肾组织中可提取的成熟EGF水平升高，膜相关EGF前体水平降低。在损伤诱导之前或之后立即给大鼠注射三碘甲腺原氨酸(T3)，并没有进一步增加可提取的EGF水平。急性脑缺血损伤后24 h，肾脏EGF mRNA表达水平降低，但不受T3影响。与正常大鼠肾膜相比，伤后24 h大鼠肾膜EGF前体分泌成熟EGF的能力明显增强。此外，肾损伤后24小时，肾组织中甲状腺激素5‘-脱碘酶活性升高。循环总甲状腺素(T4)、游离T4和游离T3水平降低。总三碘甲腺原氨酸没有变化。正常大鼠给予T3后，肾脏5‘-脱碘酶活性增加，EGF前体裂解增加。给予丙基硫氧嘧啶可抑制大鼠肾脏5‘-脱碘酶活性，并阻止可提取的EGF缺血后损伤的增加。我们的结论是，大鼠缺血后肾脏可提取的成熟EGF水平的增加是由于裂解EGF前体的丝氨酸蛋白酶活性增强所致。这种活性可能是由肾脏产生的T_3刺激的。肾脏T4代谢和EGF表达的这些变化可能有助于缺血后肾功能的恢复。
To define the relationship between renal epidermal growth factor (EGF) expression and thyroid hormones in acute renal failure, we performed an analysis of the renal thyroid hormone-EGF axis following acute ischemic renal injury in rats. Levels of mature EGF extractable from kidney were elevated 24 h postinjury, and levels of membrane-associated EGF precursor were reduced. Administration of triodothyronine (T3) to rats, either prior to or immediately following the induction of injury, did not further increase levels of extractable EGF. Levels of EGF mRNA in kidneys were reduced 24 h following acute ischemic damage and not affected by administration of T3. Enhanced production of mature EGF from EGF precursor occurred in membranes isolated from kidneys of rats 24 h postinjury compared with production in membranes from kidneys of normal rats. In addition, levels of thyroxine 5'-deiodinase activity in renal membranes were increased 24 h following injury. Levels of circulating total thyroxine (T4), free T4, and free T3 were reduced postischemic injury. Total T3 was unchanged. The administration of T3 to normal rats increased renal 5'-deiodinase activity and EGF precursor cleavage. Administration of propylthiouracil to rats inhibited renal 5'-deiodinase activity and prevented the increase in extractable EGF postischemic injury. We conclude that the increase in levels of mature EGF extractable from kidneys of rats postischemic injury results from enhanced activity of the serine protease that cleaves the EGF precursor. This activity may be stimulated by T3 produced in kidney. These alterations in renal T4 metabolism and EGF expression could serve to facilitate recovery of renal function following ischemia.