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   human carnosinase 1 overexpression aggravates diabetes and renal impairment in btbrob/ob mice  
   
نویسنده qiu jiedong ,albrecht thomas ,zhang shiqi ,hauske sibylle j. ,rodriguez-niño angelica ,zhang xinmiao ,nosan darya ,pastene diego o. ,sticht carsten ,delatorre carolina ,goor harry van ,porubsky stefan ,krämer bernhard k. ,yard benito a.
منبع journal of molecular medicine - 2020 - دوره : 98 - شماره : 9 - صفحه:1333 -1346
چکیده    To assess the influence of serum carnosinase (cn1) on the course of diabetic kidney disease (dkd). hcn1 transgenic (tg) mice were generated in a btbrob/ob genetic background to allow the spontaneous development of dkd in the presence of serum carnosinase. the influence of serum cn1 expression on obesity, hyperglycemia, and renal impairment was assessed. we also studied if aggravation of renal impairment in hcn1 tg btbrob/ob mice leads to changes in the renal transcriptome as compared with wild-type btbrob/ob mice. hcn1 was detected in the serum and urine of mice from two different hcn1 tg lines. the transgene was expressed in the liver but not in the kidney. high cn1 expression was associated with low plasma and renal carnosine concentrations, even after oral carnosine supplementation. obese hcn1 transgenic btbrob/ob mice displayed significantly higher levels of glycated hemoglobin, glycosuria, proteinuria, and increased albumin-creatinine ratios (1104 ± 696 vs 492.1 ± 282.2 μg/mg) accompanied by an increased glomerular tuft area and renal corpuscle size. gene-expression profiling of renal tissue disclosed hierarchical clustering between btbrob/wt, btbrob/ob, and hcn1 btbrob/ob mice. along with aggravation of the dkd phenotype, 26 altered genes have been found in obese hcn1 transgenic mice; among them claudin-1, thrombospondin-1, nephronectin, and peroxisome proliferator–activated receptor-alpha have been reported to play essential roles in dkd. our data support a role for serum carnosinase 1 in the progression of dkd. whether this is mainly attributed to the changes in renal carnosine concentrations warrants further studies.
کلیدواژه diabetic nephropathy ,carnosine ,antioxidants ,transgenic mice ,gene expression profiling
آدرس university hospital mannheim, heidelberg university, 5th medical department, germany. university medical centre groningen and university of groningen, department of pathology and medical biology, the netherlands, university hospital mannheim, heidelberg university, 5th medical department, germany, university hospital mannheim, heidelberg university, 5th medical department, germany. the first affiliated hospital of anhui medical university, department of endocrinology, china, university hospital mannheim, heidelberg university, 5th medical department, germany, university hospital mannheim, heidelberg university, 5th medical department, germany, university hospital mannheim, heidelberg university, 5th medical department, germany, university hospital mannheim, heidelberg university, 5th medical department, germany, university hospital mannheim, heidelberg university, 5th medical department, germany, university hospital mannheim, heidelberg university, germany, university hospital mannheim, heidelberg university, germany, university medical centre groningen and university of groningen, department of pathology and medical biology, the netherlands, university medical center of the johannes gutenberg university mainz, institute of pathology, germany, university hospital mannheim, heidelberg university, 5th medical department, germany. european center for angioscience, germany, university hospital mannheim, heidelberg university, 5th medical department, germany. european center for angioscience, germany
 
     
   
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