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

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.

• Authors: 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, Hiroshi Itoh
• Journal: Current hypertension reviews (Curr Hypertens Rev) Vol. 12 Issue 2 Pg. 95-104 ( 2016) ISSN: 1875-6506 [Electronic] United Arab Emirates
• PMID: 26931474 (Publication Type: Journal Article, Review)

Chemical References

• Claudin-1
• Nicotinic Acids
• Nicotinamide Mononucleotide
• SIRT1 protein, human
• Sirtuin 1

Topics

• Albuminuria (metabolism, physiopathology)
• Cell Communication (physiology)
• Claudin-1 (metabolism)
• Diabetic Nephropathies (metabolism)
• Epithelial Cells (metabolism)
• Kidney Glomerulus (metabolism)
• Kidney Tubules, Proximal (cytology, metabolism)
• Nicotinamide Mononucleotide (metabolism)
• Nicotinic Acids (metabolism)
• Podocytes (metabolism)
• Sirtuin 1 (metabolism)