Long-term expression of glomerular genes in diabetic nephropathy
| العنوان: | Long-term expression of glomerular genes in diabetic nephropathy |
|---|---|
| المؤلفون: | Franz Josef Putz, Sebastian Beck, Bernhard Banas, Christoph Moehle, Thomas Stempfl, Simone Reichelt-Wurm, Dominik Chittka, Laura Lennartz, Kathrin Eidenschink, Miriam C. Banas |
| المصدر: | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 33(9) |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_specialty, Microarray, Renal cortex, Kidney Glomerulus, Mice, Obese, 030209 endocrinology & metabolism, Mice, Inbred Strains, Type 2 diabetes, Polymerase Chain Reaction, Diabetes Mellitus, Experimental, Diabetic nephropathy, Pathogenesis, 03 medical and health sciences, Mice, 0302 clinical medicine, Internal medicine, Diabetes mellitus, medicine, Animals, Diabetic Nephropathies, Regulation of gene expression, Transplantation, Kidney, business.industry, Podocytes, medicine.disease, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Gene Expression Regulation, Nephrology, RNA, business |
| الوصف: | Background Although diabetic nephropathy (DN) is the most common cause for end-stage renal disease in western societies, its pathogenesis still remains largely unclear. A different gene pattern of diabetic and healthy kidney cells is one of the probable explanations. Numerous signalling pathways have emerged as important pathophysiological mechanisms for diabetes-induced renal injury. Methods Glomerular cells, as podocytes or mesangial cells, are predominantly involved in the development of diabetic renal lesions. While many gene assays concerning DN are performed with whole kidney or renal cortex tissue, we isolated glomeruli from black and tan, brachyuric (BTBR) obese/obese (ob/ob) and wildtype mice at four different timepoints (4, 8, 16 and 24 weeks) and performed an mRNA microarray to identify differentially expressed genes (DEGs). In contrast to many other diabetic mouse models, these homozygous ob/ob leptin-deficient mice develop not only a severe type 2 diabetes, but also diabetic kidney injury with all the clinical and especially histologic features defining human DN. By functional enrichment analysis we were able to investigate biological processes and pathways enriched by the DEGs at different disease stages. Altered expression of nine randomly selected genes was confirmed by quantitative polymerase chain reaction from glomerular RNA. Results Ob/ob type 2 diabetic mice showed up- and downregulation of genes primarily involved in metabolic processes and pathways, including glucose, lipid, fatty acid, retinol and amino acid metabolism. Members of the CYP4A and ApoB family were found among the top abundant genes. But more interestingly, altered gene loci showed enrichment for processes and pathways linked to angioneogenesis, complement cascades, semaphorin pathways, oxidation and reduction processes and renin secretion. Conclusion The gene profile of BTBR ob/ob type 2 diabetic mice we conducted in this study can help to identify new key players in molecular pathogenesis of diabetic kidney injury. |
| تدمد: | 1460-2385 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3a1e0795a7bd423e92b534df3d0b04a6 https://pubmed.ncbi.nlm.nih.gov/29340699 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3a1e0795a7bd423e92b534df3d0b04a6 |
| قاعدة البيانات: | OpenAIRE |
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