New targets for treatment of diabetic nephropathy: What we have learned from animal models

Frank C. Brosius, Charles E. Alpers

Research output: Contribution to journalReview articlepeer-review

40 Scopus citations

Abstract

Purpose of Review: There has been an advance in our understanding of the mechanisms of diabetic nephropathy over the past few years and much of that has occurred because of studies in animal models of diabetic nephropathy. Recent Findings: Studies in animal models of diabetic nephropathy, especially in mice, have underlined the multifactorial nature of the pathogenesis of the disease process and the recognition that these models only partly replicate the changes found in human disease. Despite these limitations, recent animal model studies have identified a number of new, specific molecular abnormalities that point to pathways and specific molecules as potential targets for preventive or therapeutic intervention. These specific targets include the diabetic nephropathy related decreases in endothelial nitric oxide synthase activity and renal dopamine production and the increases in Nrf-2, JAK/STAT, and mammalian target of rapamycin complex 1 signaling. These and other altered signaling pathways are described in this review. We emphasize the use of a unique investigative resource, Nephromine, to utilize a library of mRNA expression data obtained from the kidney biopsies of humans with diabetic nephropathy, to compare and validate findings in mouse models with human disease. Summary: Several new pathways have been implicated in the progression of diabetic nephropathy through studies of animal models. Some of these appear to be altered in human diabetic nephropathy and may be targets for therapy.

Original languageEnglish (US)
Pages (from-to)17-25
Number of pages9
JournalCurrent Opinion in Nephrology and Hypertension
Volume22
Issue number1
DOIs
StatePublished - Jan 2013
Externally publishedYes

Keywords

  • diabetic kidney disease
  • signaling
  • transgenic mouse

ASJC Scopus subject areas

  • Internal Medicine
  • Nephrology

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