Communication from Tubular Epithelial Cells to Podocytes through Sirt1 and Nicotinic Acid Metabolism
Communication from Tubular Epithelial Cells to Podocytes through Sirt1 and Nicotinic Acid Metabolism
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DOI：
10.2174/1573402112666160302102217
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发表时间：
2016-01-01
影响因子：
2.3
通讯作者：
Itoh, Hiroshi
中科院分区：
文献类型：
--
作者：
Hasegawa, Kazuhiro;Wakino, Shu;Itoh, Hiroshi
我们最近发表了肾小管上皮细胞通过烟酸代谢影响糖尿病肾病（DN）足细胞表观基因组，我们将这种关系命名为“近端肾小管-足细胞通讯”。本文就Sirt 1在DN早期的作用机制及其与烟酸代谢的关系作一综述。我们主要讨论以下三个发现。首先，我们描述了近端小管-足细胞通讯的细节。其次，我们解释了Sirt 1如何通过表观遗传机制调节蛋白尿。这意味着反复的高糖应激触发了近端小管的初始变化，从而导致表观遗传学上不可逆的肾小球损伤。然而，近端小管Sirt 1过表达可以挽救这些变化。我们以前的数据表明，近端小管中Sirt 1表达的减少导致肾小球Sirt 1的减少和随后的肾小球Claudin-1的增加。这似乎是合理的，一些体液介质从近端小管释放，迁移到足细胞和肾小球，并影响Sirt 1在足细胞中的表达。第三，我们提到了一种连接这种通信的介质，烟酰胺单核苷酸（NMN）。我们认为Sirt 1或NMN不仅可以作为治疗靶点，而且可以作为早期DN的预后标志物。
We have recently published that tubular epithelial cells affect the podocyte epigenome though nicotinic acid metabolism in diabetic nephropathy (DN), and we have named this relationship "proximal tubule-podocyte communication". In this review, we describe this novel mechanism in the early stage of DN, focusing on the function of renal tubular Sirt1 and Sirt1-related nicotinic acid metabolism. Mainly, we discuss the following three findings. First, we described the details of proximal tubule-podocyte communication. Second, we explained how Sirt1 regulates albuminuria via epigenetic mechanisms. This means that repeated high glucose stress triggers the initial changes in proximal tubules, which lead to the epigenetically irreversible glomerular damages. However, proximal tubular Sirt1 overexpression can rescue these changes. Our previous data indicated that the decrease in Sirt1 expression in proximal tubules caused the reduction in glomerular Sirt1 and the subsequent increase in glomerular Claudin-1. It seemed plausible that some humoral mediator is released from proximal tubules, migrates to podocytes and glomeruli, and affects Sirt1 expression in podocytes. Third, we mentioned a mediator connecting this communication, nicotinamide mononucleotide (NMN). We suggest the potential of Sirt1 or NMN as not only a therapeutic target but also as a prognostic marker of very early stage DN.