| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Nephrology Dialysis Transplantation | ||||
| Publisher: | Oxford Univ. Press | ||||
| Place of Publication: | OXFORD | ||||
| Date: | 2018 | ||||
| Institutions: | Medicine > Abteilung für Nephrologie | ||||
| Identification Number: |
| ||||
| Keywords: | PODOCYTE-SECRETED ANGIOPOIETIN-LIKE-4; CHRONIC KIDNEY-DISEASE; OXIDATIVE STRESS; INJURY; CYTOCHROME-P450; MECHANISMS; NEUROPILIN-1; ASSOCIATION; PROTEINURIA; METABOLISM; BTBR ob/ob mice; diabetic nephropathy; genetic profile; mRNA microarray | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 46829 |
Web of ScienceAbstract
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. ...
Abstract
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 polymerise 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.
Metadata last modified: 11 Aug 2021 12:15
Altmetric