Conclusions and Perspectives
In various types of renal diseases, including both diabetic- and non-diabetic disorders, RAGE and its ligands are commonly observed to be dysregulated. The major problem of these phenomena in renal diseases might be the vicious cycle that impairs kidney by increased AGEs or when other RAGE ligands fail to remove them, causing these ligands to accumulate and the relevant signals to accelerate. Therefore, numerous studies suggest RAGE and its ligands as new potential targets for the diagnosis, monitoring, and treatment of renal diseases that have abnormal regulation of them. Firstly, ligands expression or secretion level can be used as a diagnostic or staging marker. S100B is already used in evaluations after treatment of melanoma in a clinical setting [51]. Secondly, more trials targeting RAGE ligands either with inhibitors of them or the soluble form of RAGE have been reported. Soluble RAGE treatment significantly alleviates the symptoms of nephritis in vivo [52], and in cancer studies, nude mice injected with soluble RAGE-over-expressing cells have shown remarkable inhibition of tumor formation [53]. With inhibitors of AGEs, several agents, including aminoguanidine and pyridoxamine, have been tried in humans; some of them have shown enhanced renal function in diabetic patients, but these trials were terminated early because of safety concerns [54, 55]. Finally, more recently, epigenetic regulation by microRNAs of molecules involved in RAGE signaling pathways is also being studied [56].