title: New targets for treatment of diabetic nephropathy:  what we have learned from animal models.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109-0676, USA. fbrosius@umich.edu
authors.forename: Frank C
authors.initials: FC
authors.lastname: Brosius
authors.forename: Charles E
authors.initials: CE
authors.lastname: Alpers
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000209:etiology / Q000378:metabolism*; D004298:Dopamine / Q000096:biosynthesis; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D019255:NADPH Oxidases / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D054411:Receptors, Leptin / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
chemical_list: D019485:Bone Morphogenetic Proteins; D020738:Leptin; D046912:Multiprotein Complexes; D051267:NF-E2-Related Factor 2; D011506:Proteins; D054411:Receptors, Leptin; D050791:STAT Transcription Factors; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; D053612:Janus Kinases; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D004298:Dopamine