title: Effect of dietary salt on regulation of TGF-β in the kidney.
abstract: Dietary sodium chloride (salt) has long been considered injurious to the kidney by promoting the development of glomerular and tubulointerstitial fibrosis. Endothelial cells throughout the vasculature and glomeruli respond to increased dietary salt intake with increased production of transforming growth factor-β (TGF-β) and nitric oxide. High-salt intake activates large-conductance, voltage- and calcium-activated potassium (BK(Ca)) channels in endothelial cells. Activation of BK(Ca) channels promotes signaling through proline-rich tyrosine kinase-2, cellular-sarcoma (c-Src), Akt (also known as protein kinase B), and mitogen-activated protein kinase pathways that lead to endothelial production of TGF-β and nitric oxide. TGF-β signaling is broadly accepted as a strong stimulator of renal fibrosis. The classic description of TGF-β signaling pathology in renal disease involves signaling through Smad proteins resulting in extracellular matrix deposition and fibrosis. Active TGF-β1 also causes fibrosis by inducing epithelial-mesenchymal transition and apoptosis. By enhancing TGF-β signaling, increased dietary salt intake leads to progressive renal failure from nephron loss and glomerular and tubulointerstitial fibrosis.
authors: Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors: Michael B
authors: MB
authors: Hovater
authors: Paul W
authors: PW
authors: Sanders
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005355:Fibrosis; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D007676:Kidney Failure, Chronic / Q000378:metabolism; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D051785:Smad Proteins; D017673:Sodium Chloride, Dietary; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D009569:Nitric Oxide; D051418:Focal Adhesion Kinase 2; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases