title: 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.affiliation: Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjukuku, Tokyo 160-8582, Japan. kazuhiro@z2.keio.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Shu
authors.initials: S
authors.lastname: Wakino
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sakamaki
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Muraoka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Umino
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Minakuchi
authors.forename: Ayumi
authors.initials: A
authors.lastname: Yoshifuji
authors.forename: Makiko
authors.initials: M
authors.lastname: Naitoh
authors.forename: Keisuke
authors.initials: K
authors.lastname: Shinozuka
authors.forename: Koji
authors.initials: K
authors.lastname: Futatsugi
authors.forename: Hidenori
authors.initials: H
authors.lastname: Urai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kanda
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Tokuyama
authors.forename: Koichi
authors.initials: K
authors.lastname: Hayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
mesh_terms: D000419:Albuminuria / Q000378:metabolism / Q000503:physiopathology; D002450:Cell Communication / Q000502:physiology*; D062445:Claudin-1 / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000378:metabolism; D009537:Nicotinamide Mononucleotide / Q000378:metabolism; D009539:Nicotinic Acids / Q000378:metabolism*; D050199:Podocytes / Q000378:metabolism*; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D062445:Claudin-1; D009539:Nicotinic Acids; D009537:Nicotinamide Mononucleotide; C447939:SIRT1 protein, human; D056564:Sirtuin 1