Expression of angiotensin II type 1 receptor-interacting molecule in normal human kidney and IgA nephropathy
Expression of angiotensin II type 1 receptor-interacting molecule in normal human kidney and IgA nephropathy
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DOI：
10.1152/ajprenal.00667.2009
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发表时间：
2010-10-01
影响因子：
4.2
通讯作者：
Umemura, Satoshi
中科院分区：
文献类型：
--
作者：
Masuda, Shin-ichiro;Tamura, Kouichi;Umemura, Satoshi
Masuda S, Tamura K, Wakui H, Maeda A, Dejima T, Hirose T, Toyoda M, Azuma K, Ohsawa M, Kanaoka T, Yanagi M, Yoshida S, Mitsuhashi H, Matsuda M, Ishigami T, Toya Y, Suzuki D, Nagashima Y, Umemura S. 血管紧张素 II 1 型的表达 正常人肾脏和 IgA 肾病中的受体相互作用分子。 Am J Physiol Renal Physiol 299：F720-F731，2010。首次发表于 2010 年 8 月 4 日； doi:10.1152/ajprenal.00667.2009.-肾内肾素-血管紧张素系统通过激活血管、肾小球和肾小管血管紧张素 II 1 型 (AT(1)) 受体信号传导，在肾循环和钠重吸收的调节中发挥着至关重要的作用。我们之前克隆了一种与鼠 AT(1) 受体特异性相互作用以抑制 AT(1) 受体信号传导的分子，我们将其命名为 ATRAP（AT(1) 受体相关蛋白）。由于小鼠 ATRAP 在肾脏中高表达，在本研究中，我们研究了人 ATRAP 在正常肾脏和 IgA 肾病患者肾活检标本中的表达和分布。在正常人肾脏中，ATRAP mRNA和蛋白质沿着肾小管从鲍曼囊到髓质集合管广泛而丰富地分布。在所有肾小管上皮细胞中，ATRAP 蛋白与 AT(1) 受体共定位。在 IgA 肾病肾活检标本中，观察到 ATRAP 和 AT(1) 受体基因表达呈显着正相关。 IgA 肾病患者的肾小管间质 ATRAP 表达与估计肾小球滤过率之间也存在正相关。此外，我们使用小鼠远曲小管细胞（mDCT）的永生化细胞系检查了肾小管 AT（1）受体的功能，发现通过腺病毒基因转移过度表达 ATRAP 抑制了 mDCT 细胞中血管紧张素 II 介导的转化生长因子-β 产生的增加。这些发现表明，ATRAP 可能在 IgA 肾病中通过反调节作用与 AT(1) 受体协同平衡肾脏肾素-血管紧张素系统，并提出管状 ATRAP 对 AT(1) 受体信号传导的拮抗作用。
Masuda S, Tamura K, Wakui H, Maeda A, Dejima T, Hirose T, Toyoda M, Azuma K, Ohsawa M, Kanaoka T, Yanagi M, Yoshida S, Mitsuhashi H, Matsuda M, Ishigami T, Toya Y, Suzuki D, Nagashima Y, Umemura S. Expression of angiotensin II type 1 receptor-interacting molecule in normal human kidney and IgA nephropathy. Am J Physiol Renal Physiol 299: F720-F731, 2010. First published August 4, 2010; doi:10.1152/ajprenal.00667.2009.-The intrarenal renin-angiotensin system plays a crucial role in the regulation of renal circulation and sodium reabsorption through the activation of vascular, glomerular, and tubular angiotensin II type 1 (AT(1)) receptor signaling. We previously cloned a molecule that specifically interacted with the murine AT(1) receptor to inhibit AT(1) receptor signaling, which we named ATRAP (for AT(1) receptor-associated protein). Since murine ATRAP was shown to be highly expressed in the kidney, in the present study we investigated expression and distribution of human ATRAP in normal kidney and renal biopsy specimens from patients with IgA nephropathy. In the normal human kidney, both ATRAP mRNA and protein were widely and abundantly distributed along the renal tubules from Bowman's capsule to the medullary collecting ducts. In all renal tubular epithelial cells, the ATRAP protein colocalized with the AT(1) receptor. In renal biopsy specimens with IgA nephropathy, a significant positive correlation between ATRAP and AT(1) receptor gene expression was observed. There was also a positive relationship between tubulointerstitial ATRAP expression and the estimated glomerular filtration rate in patients with IgA nephropathy. Furthermore, we examined the function of the tubular AT(1) receptor using an immortalized cell line of mouse distal convoluted tubule cells (mDCT) and found that overexpression of ATRAP by adenoviral gene transfer suppressed the angiotensin II-mediated increases in transforming growth factor-beta production in mDCT cells. These findings suggest that ATRAP might play a role in balancing the renal renin-angiotensin system synergistically with the AT(1) receptor by counterregulatory effects in IgA nephropathy and propose an antagonistic effect of tubular ATRAP on AT(1) receptor signaling.