Does a β2-adrenergic receptor-WNK4-Na-Cl co-transporter signal cascade exist in the in vivo kidney?
Does a β2-adrenergic receptor-WNK4-Na-Cl co-transporter signal cascade exist in the in vivo kidney?
复制标题
体内肾脏中是否存在β2-肾上腺素受体-WNK4-Na-Cl协同转运蛋白信号级联？
DOI：
10.1038/nm.2809
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
Uchida S
中科院分区：
文献类型：
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作者：
Aoki T.;他;Hara-Chikuma M;Hossain Khan MZ;Iimori S;Iimori S;Kanda E;Magdeldin S;Mandai S;Nishida H;Ohtaki H;Oi K;Sasaki S.;Susa K;Susa K;Uchida S
在他们的信件中，内田等人。回应我们的论文2，其中我们表明肾脏 β2-肾上腺素能受体刺激下调 WNK4 表达并上调 Na-Cl 协同转运蛋白 (NCC) 表达，从而促进盐敏感性高血压的发展。我们赞赏 Uchida 等人的研究。 1 及其研究结果证实了我们的原始数据，即去甲肾上腺素治疗有助于盐敏感性高血压的发展，其疗效与我们的研究相似2。然而，他们没有检测到去甲肾上腺素刺激后肾脏中 WNK4 或 NCC mRNA 或蛋白质水平有任何变化1。如图1所示，我们首先重新检查WNK4 mRNA水平在去甲肾上腺素刺激下是否降低。这两项研究之间明显的方法学差异是 Uchida 等人。 1 人进行了为期 1 周的盐饮食实验，与我们的 3 天方案形成对比；因此，我们在 1 周的盐饮食后进行了所有额外的实验。我们收集了 RNA 样本，并通过定量 RT-PCR 和 Northern blotting 对其进行了分析（图 1a、b）。在他们的研究中，内田等人。 1 选择了与我们研究中使用的不同的引物组2（ABI Mm00841400_m1
In their correspondence1, Uchida et al. respond to our paper2 in which we showed that renal β2-adrenergic receptor stimulation downregulates WNK4 expression and upregulates Na-Cl co-transporter (NCC) expression, hence contributing to the development of salt sensitive hypertension. We appreciate the study of Uchida et al. 1 and their findings, which confirm our original data that norepinephrine treatment contributes to the development of salt-sensitive hypertension, with a similar efficacy as in our study2. However, they did not detect any changes in WNK4 or NCC mRNA or protein levels in the kidney upon norepinephrine stimulation1.To address the concerns raised by Uchida et al. 1, we first reexamined whether WNK4 mRNA levels are decreased under norepinephrine stimulation. An obvious methodological difference between the two studies is that Uchida et al. 1 performed their salt diet experiments for 1 week in contrast to our 3-d regimen; we therefore performed all additional experiments after 1 week of salt diet. We collected RNA samples and analyzed them by both quantitative RT-PCR and northern blotting (Fig. 1a, b). In their study, Uchida et al. 1 chose a different primer set from the one used in our study2 (the ABI Mm00841400_m1