New insights into the mechanisms of fibrosis and sclerosis in diabetic nephropathy.
Progression of diabetic nephropathy (DN) is manifested by gradual scarring of both the renal glomerulus and tubulointerstitial region. Over the past several years, the general understanding of the pathogenic factors that lead to renal fibrosis in DN has expanded considerably. In this review, some of the important factors that appear to be involved in driving this fibrosing process are discussed, with special emphasis on newer findings and insights. It is now clear that multiple cell types in the kidney contribute to progressive fibrosis in DN. New concepts about bradykinin, TGF-beta and eNOS signaling as well as JAK/STAT activation and the central role of inflammation in both glomerular and tubulointerstitial fibrosis are discussed.
Brosius
Frank C
FC
Departments of Internal Medicine, and Molecular and Integrative Physiology, University of Michigan Medical School, 5520 MSRB1, 1150 W. Medical Center Drive, Ann Arbor, MI, 48109-0680, USA. fbrosius@umich.edu
D000818:Animals; D065094:Bradykinin B2 Receptor Antagonists; D003928:Diabetic Nephropathies / Q000473:pathology*; D018450:Disease Progression; D015777:Eicosanoids / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D007249:Inflammation / Q000150:complications; D053612:Janus Kinases / Q000378:metabolism; D007668:Kidney / Q000473:pathology*; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D050356:Lipid Metabolism; D035683:MicroRNAs / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011486:Protein C / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D012598:Sclerosis; D016212:Transforming Growth Factor beta / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D065094:Bradykinin B2 Receptor Antagonists; D015777:Eicosanoids; D035683:MicroRNAs; D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; C051321:SERPINE1 protein, human; D050791:STAT Transcription Factors; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D053612:Janus Kinases