Communication from Tubular Epithelial Cells to Podocytes through Sirt1 and Nicotinic Acid Metabolism

Title:Communication from Tubular Epithelial Cells to Podocytes through Sirt1 and Nicotinic Acid Metabolism

Volume: 12 Issue: 2

Author(s): Kazuhiro Hasegawa, Shu Wakino, Yusuke Sakamaki, Hirokazu Muraoka, Hiroyuki Umino, Hitoshi Minakuchi, Ayumi Yoshifuji, Makiko Naitoh, Keisuke Shinozuka, Koji Futatsugi, Hidenori Urai, Takeshi Kanda, Hirobumi Tokuyama, Koichi Hayashi and Hiroshi Itoh

Affiliation:

Keywords: Sirtuin, Sirt1, Claudin-1, NMN, and diabetic nephropathy.

Abstract: 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.

Cite this article as:

Hasegawa Kazuhiro, Wakino Shu, Sakamaki Yusuke, Muraoka Hirokazu, Umino Hiroyuki, Minakuchi Hitoshi, Yoshifuji Ayumi, Naitoh Makiko, Shinozuka Keisuke, Futatsugi Koji, Urai Hidenori, Kanda Takeshi, Tokuyama Hirobumi, Hayashi Koichi and Itoh Hiroshi, Communication from Tubular Epithelial Cells to Podocytes through Sirt1 and Nicotinic Acid Metabolism, Current Hypertension Reviews 2016; 12 (2) . https://dx.doi.org/10.2174/1573402112666160302102217