Title:Targeting Adenosine Signaling to Treatment of Diabetic Nephropathy
Volume: 14
Issue: 4
Author(s): Claudia Quezada, Sebastian Alarcon, Catherinne Jaramillo, Daniel Munoz, Carlos Oyarzun and Rody San Martin
Affiliation:
Keywords:
Adenosine, adenosine A2B receptor, diabetic nephropathy, equilibrative nucleoside transporters
Abstract: Diabetic nephropathy (DN) continues being the primary cause of chronic hemodialysis and terminal renal disease
worldwide. At tissue levels the DN occurs with glomerulopathy affecting the integrity of the filtration barrier and
with an extensive glomerular and tubule-interstitial fibrosis. Current available therapeutic approaches have only demonstrated
a modest effect on progression of kidney injury. Therefore, more research concerning the pathomechanisms and
possible interventions are needed. Interestingly, in the last years it has been documented that DN progresses with growing
levels of the nucleoside adenosine. This finding increased the interest in the events controlling the extracellular levels of
the nucleoside. While the metabolism of extracellular ATP and cyclic AMP are well recognized sources, evidences regarding
the role of the equilibrative nucleoside transporters in controlling adenosine availability and promoting diabetic
glomerulopathy have recently acquired a pivotal role. The physiological effects of nucleoside are mediated by the P1 family
of adenosine receptors. It has been shown in vivo that the use of an antagonist of the A2B receptor subtype can block
the most remarkable early alterations seen in diabetic glomerulopathy. Furthermore, using models of chronic kidney injury
it was demonstrated that fibrosis can also be blocked using treatment with the antagonist of A2B receptor subtype.
This review highlights these findings that correlate the activity of a low affinity adenosine receptor with an increase in the
ligand availability in the pathological state. In addition, we discuss the possible therapeutic interventions of adenosine signaling
with regards to DN treatment.
