Abstract
Diabetic nephropathy (DN), a common diabetic microvascular complication, is characterized by progressive glomerular sclerosis and tubulointerstitial fibrosis. However, the underlying mechanisms involved in DN remain to be elucidated. We explored changes in the transcriptional profile in spontaneous type 2 diabetic db/db mice by using the cDNA microarray. Compared with control db/m mice, the db/db mice exhibited marked increases in body weight, kidney weight, and urinary albumin excretion. Renal histological analysis revealed mesangial expansion and thickness of the basement membrane in the kidney of the db/db mice. A total of 355 differentially expressed genes (DEGs) were identified by microarray analysis. Pathway enrichment analysis suggested that biological oxidation, bile acid metabolism, and steroid hormone synthesis were the 3 major significant pathways. The top 10 hub genes were selected from the constructed PPI network of DEGs, including Ccnb2 and Nr1i2, which remained largely unclear in DN. We believe that our study can help elucidate the molecular mechanisms underlying DN.
Highlights
With the increasing prevalence of diabetes worldwide, diabetic nephropathy, a serious and major microvascular complication of diabetes mellitus (DM), has become a global problem affecting about 40% of patients with diabetes and is the primary cause of end-stage renal diseases (ESRD) in developed countries [1, 2]
Diabetic nephropathy (DN) is characterized by excessive accumulation of extracellular matrix (ECM) with thickening of glomerular and tubular basement membranes and increased mesangial materials [3]
Body weight and blood glucose in db/db mice were markedly higher than those in db/m mice. Compared with those of the control db/m mice, significant increases in 24 h urinary albumin and kidney weight were indicated in the db/db mice
Summary
With the increasing prevalence of diabetes worldwide, diabetic nephropathy, a serious and major microvascular complication of diabetes mellitus (DM), has become a global problem affecting about 40% of patients with diabetes and is the primary cause of end-stage renal diseases (ESRD) in developed countries [1, 2]. To fundamentally understand and elucidate the mechanism of DN, high-throughput microarrays could be used to investigate the underlying genetic characteristic of processes involved in DN. These techniques have been widely used in screening the potential targets for DN. Microarray analysis can effectively identify key molecular events and pathways involved in DN. Db/db mice are commonly used to investigate the mechanisms of renal injury associated with type 2 diabetes [8]. We employed global microarray analysis combined with bioinformatics to explore the differential gene expression in db/db and db/m mice in order to identify candidate genes that may be involved in the development of DN
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