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.