Expression of adrenomedullin 2/intermedin, a possible reno-protective peptide, is decreased in the kidneys of rats with hypertension or renal failure
Expression of adrenomedullin 2/intermedin, a possible reno-protective peptide, is decreased in the kidneys of rats with hypertension or renal failure
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DOI：
10.1152/ajprenal.00679.2009
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发表时间：
2010-07-01
影响因子：
4.2
通讯作者：
Imai, Yutaka
中科院分区：
文献类型：
--
作者：
Hirose, Takuo;Totsune, Kazuhito;Imai, Yutaka
Hirose T，Totsune K，Mori N，Mori T，Morimoto R，Metoki H，Asayama K，Kikuya M，Ohkubo T，Kohzuki M，Takahashi K，Imai Y。高血压或肾功能衰竭大鼠肾脏肾上腺髓质素2/中间体素表达减少。Am J Physiol肾脏生理学299：F128-F134,2010。首次发表于2010年5月12日；DOI：10.1152/ajprenal.00679.2009。-肾上腺髓质素2/间质(AM2/imd)是一种具有器官保护作用的有效血管扩张多肽，在肾脏中大量表达。我们用定量RT-PCR、放射免疫分析和免疫组织化学方法检测了AM2/IMD在高血压或慢性肾损伤大鼠肾脏中的表达。将8周龄雄性自发性高血压大鼠(SHR)和Wistar-京都(WKY)大鼠的肾脏解剖为内髓、外髓、皮质和肾小球部分。采用WKY大鼠5/6肾切除法制备大鼠肾损伤模型。AM2/IMD基因在四个肾脏部分中以皮质表达最高，而在所有肾脏部分，SHR均显著低于WKY大鼠。与假手术组比较，5/6肾切除后3天和56天大鼠残肾中AM2/IMD基因表达水平显著降低，而构成AM和AM2/IMD受体的降钙素受体样受体、受体活性修饰蛋白-1和受体活性修饰蛋白-2的基因表达水平显著升高。AM基因表达在肾切除后第3天下降，在第56天升高。放射免疫分析证实5/6肾切除后第56天大鼠残肾AM2/IMD免疫活性降低。用抗AM2/IMD抗体对肾小管进行免疫组织化学染色，5/6肾切除大鼠肾小管上皮细胞AM2/IMD免疫染色较假手术组减少。综上所述，自发性高血压大鼠和5/6肾切除大鼠肾内AM2/IMD表达减少。鉴于AM2/IMD的器官保护作用，AM2/IMD作为一种内源性调节肽的下调可能在肾损害的进展中起作用。
Hirose T, Totsune K, Mori N, Mori T, Morimoto R, Metoki H, Asayama K, Kikuya M, Ohkubo T, Kohzuki M, Takahashi K, Imai Y. Expression of adrenomedullin 2/intermedin, a possible reno-protective peptide, is decreased in the kidneys of rats with hypertension or renal failure. Am J Physiol Renal Physiol 299: F128-F134, 2010. First published May 12, 2010; doi: 10.1152/ajprenal.00679.2009.-Adrenomedullin 2/intermedin (AM2/IMD) is a potent vasodilator peptide with organ-protective effects and is abundantly expressed in the kidney. We examined the expression of AM2/IMD in the kidneys of rats with hypertension or chronic renal impairment using quantitative RT-PCR, radioimmunoassay, and immunohistochemistry. Kidneys of 8-wk-old male spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were dissected into inner medulla, outer medulla, cortex, and glomerulus fractions. A rat renal impairment model was prepared by 5/6 nephrectomy in WKY rats. AM2/IMD mRNA levels were the highest in the cortex among four renal portions, and significantly lower in SHR than WKY rats in all renal portions. In the remnant kidneys of 5/6 nephrectomized rats, AM2/IMD mRNA levels were significantly decreased on days 3 and 56, whereas mRNA levels of calcitonin receptor-like receptor, receptor activity-modifying proteins-1 and -2, which form receptor for AM and AM2/IMD, were increased, compared with that in sham-operated rats. AM mRNA levels were decreased on day 3, but increased on day 56, after nephrectomy. Decreased immunoreactive AM2/IMD levels in the remnant kidneys of 5/6 nephrectomized rats on day 56 were confirmed by radioimmunoassay. The renal tubules were immunostained with anti-AM2/IMD antibody, with a decreased AM2/IMD immunostaining found in proximal tubular cells of 5/6 nephrectomized rats compared with sham-operated rats. In conclusion, intrarenal AM2/IMD expression is decreased in SHR and 5/6 nephrectomized rats. Given the organ-protective effects of AM2/IMD, the downregulation of AM2/IMD as an endogenous regulatory peptide may have a role in the progression of renal impairment.