The Role of Hydrogen Sulfide in Renal System

Hydrogen sulfide has gained recognition as the third gaseous signaling molecule after nitric oxide and carbon monoxide. This review surveys the emerging role of HS in mammalian renal system, with emphasis on both renal physiology and diseases. HS is produced redundantly by four pathways in kidney, indicating the abundance of this gaseous molecule in the organ. In physiological conditions, HS was found to regulate the excretory function of the kidney possibly by the inhibitory effect on sodium transporters on renal tubular cells. Likewise, it also influences the release of renin from juxtaglomerular cells and thereby modulates blood pressure. A possible role of HS as an oxygen sensor has also been discussed, especially at renal medulla. Alternation of HS level has been implicated in various pathological conditions such as renal ischemia/reperfusion, obstructive nephropathy, diabetic nephropathy, and hypertensive nephropathy. Moreover, HS donors exhibit broad beneficial effects in renal diseases although a few conflicts need to be resolved. Further research reveals that multiple mechanisms are underlying the protective effects of HS, including anti-inflammation, anti-oxidation, and anti-apoptosis. In the review, several research directions are also proposed including the role of mitochondrial HS in renal diseases, HS delivery to kidney by targeting D-amino acid oxidase/3-mercaptopyruvate sulfurtransferase (DAO/3-MST) pathway, effect of drug-like HS donors in kidney diseases and understanding the molecular mechanism of HS. The completion of the studies in these directions will not only improves our understanding of renal HS functions but may also be critical to translate HS to be a new therapy for renal diseases.