{'fraction_non_alphanumeric': 0.020361990950226245, 'fraction_numerical': 0.007239819004524887, 'mean_word_length': 5.446064139941691, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
340 Nad+-dependent deacetylase sirt3 activation inhibits diabetic kidney disease

Purpose of study Despite interventions for diabetes that seem to have some clinical benefit such as tight glucose and blood pressure control, kidney disease continues to be a problem in many of these patients. Recently mitochondrial dysfunction has been found to play an important role in the pathogenesis of kidney disease. We aimed to test the influence of one key mitochondrial protein deacetylase, Sirtuin 3 (SIRT3), as a potential target for therapy in patients with chronic kidney disease. Methods used We used kidney biopsies from human patients with and without diabetic nephropathy or glomerulopathy to measure for SIRT3 expression and activity. To test the effect of SIRT3 on the prevention of diabetic kidney disease, we conducted a study comparing three groups of mice: A control group, a diabetic group, and a diabetic group treated with an agonist for SIRT3, nicotinamide riboside (NR). We performed histopathology and immunofluorescence microscopy to visually assess the health of the kidney which included mesangial expansion, glomeruli area, collagen IV expression, and synaptopodin. We also measured for albuminuria, serum triglycerides, SOD2, acetylated lysine, and 4-HNE, all of which are markers for kidney disease progression. Summary of results SIRT3 expression and activity decreased in human glomeruli and tubules in diabetic patients compared to controls. This result was also shown in diabetic mice compared to controls. Treatment with NR in diabetic mice decreased mesangial expansion, glomeruli area, albuminuria, serum triglycerides, acetylated lysine, SOD2, and 4-HNE compared to control. Conclusions SIRT3 plays an important role in the progression of diabetic kidney disease. In human renal biopsies SIRT3 expression and activity was decreased in diabetic patients compared to the controls with similar findings in in mice as well. Furthermore, markers of kidney disease decreased in treated diabetic mice compared to the untreated diabetic mice. The results of this study show promising results about a potential pharmaceutical target to help prevent the progression of diabetic kidney disease.