title: Caveolin-1 in the Pathogenesis of Diabetic Nephropathy: Potential Therapeutic Target?
abstract: Diabetic nephropathy, a major microvascular complication of diabetes and the most common cause of end-stage renal disease, is characterized by prominent accumulation of extracellular matrix. The membrane microdomains caveolae, and their integral protein caveolin-1, play critical roles in the regulation of signal transduction. In this review we discuss current knowledge of the contribution of caveolin-1/caveolae to profibrotic signaling and the pathogenesis of diabetic kidney disease, and assess its potential as a therapeutic target.
  
  
  
  Caveolin (cav)-1 is key to facilitating profibrotic signal transduction induced by several stimuli known to be pathogenic in diabetic nephropathy, including the most prominent factors hyperglycemia and angiotensin II. Phosphorylation of cav-1 on Y14 is an important regulator of these responses. In vivo studies support a pathogenic role for caveolae in the progression of diabetic nephropathy. Targeting caveolin-1/caveolae would enable inhibition of multiple profibrotic pathways, representing a novel and potentially potent therapeutic option for diabetic nephropathy.
authors.affiliation: Department of Medicine, Division of Nephrology, St. Joseph's Hospital, McMaster University, 50 Charlton Ave E, T3311, Hamilton, ON, L8N 4A6, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Van Krieken
authors.affiliation: Department of Medicine, Division of Nephrology, St. Joseph's Hospital, McMaster University, 50 Charlton Ave E, T3311, Hamilton, ON, L8N 4A6, Canada. krepinj@mcmaster.ca.
authors.forename: Joan C
authors.initials: JC
authors.lastname: Krepinsky
mesh_terms: D000818:Animals; D021941:Caveolae / Q000502:physiology; D051242:Caveolin 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress; D015398:Signal Transduction / Q000502:physiology
chemical_list: D051242:Caveolin 1
keywords: Angiotensin II; Caveolae; Caveolin-1; Diabetic nephropathy; Extracellular matrix; Mesangial cell