ROLE OF PURINERGIC SIGNALINGS IN MURINE MODELS OF DIABETIC NEPHROPATHY

Buenos Aires

Congreso; REUNION DE SOCIEDADES DE BIOCIENCIAS; 2021

Reunión Anual SAIC, LXIX SAI, LIII REUNION ANUAL DE LA AAFE, XI REUNION ANUAL DE NANOMED -AR

380. We have previously reported that during an inflammatory or infectiousstimulus, cells sense the hypoxic environment and release tothe extracellular milieu large amounts of ATP, which functions as apro-inflammatory metabolite driving the nature of the immune response.The purinergic ectoenzymes CD39 and CD73, metabolizeextracellular ATP into adenosine, an anti-inflammatory mediator.These purinergic pathways have been studied in the context of metabolicdiseases related to kidney damage, but their role in the typeII diabetes mellitus (T2DM) nephropathy have not been completelyestablished.The objective of the present work was to study the role of CD73in the development of diabetic nephropathy employing mice devoidof CD73 activity (CD73KO) and controls B6 (WT). To this aim, wedeveloped two murine models of T2DM, feeding the mice with mediumfat diet (17%) and water 20% fructose (model A) and high fatdiet (60%) (model B) for 22 weeks, combined with a single dose ofstreptozotocin (65-100mg/kg).In both models, at the end of treatment, blood glucose levels werehigher than 190mg/dl; but, in model A KO animals gained significantlyless weight compared to the WT (p=0,0043). In model A, bothmouse strains showed comparable renal damage parameters, suchas a decrease in diuresis and a loss of more than 50% of glomerularfiltration rate as well as significantly higher values of microalbuminuria(pWT=0,0327, pKO=0,0500), and plasma creatinine (pWT=0,0159,pKO=0,0159). In contrast, in model B, diabetic KO mice show signsof improvement with a significant correction of diuresis (p=0.0346),albuminuria (p=0.0303) and proteinuria (p=0.0043) compared to diabeticWT. Furthermore, plasma and urinary creatinine from diabeticKO mice did not show significant differences respect to healthy KO(p=0.556, p=0.9667). In conclusion, the results suggest that CD73activity could have a protective role in the development of diabeticnephropathy in a diet dependent manner.