title: Regulation of TRPC6 ion channels in podocytes - Implications for focal segmental glomerulosclerosis and acquired forms of proteinuric diseases.
abstract: The glomerular filtration barrier is a highly specialized tri-layer structure with unique functional properties. Podocyte dysfunction and cytoskeletal disorganization leads to disruption of the slit diaphragma, and proteinuria. Inflammatory diseases involving the kidney as well as inherited podocytopathies or diabetic nephropathy cause injury of the podocyte network. Focal segmental glomerulosclerosis (FSGS) is a pathologic entity that is a common cause of nephrotic syndrome with severe proteinuria in both adults and children. Several causative genes have been identified in the pathogenesis of FSGS. Mutations of the transient receptor potential canonical-6 (TRPC6), a non-selective cation channel that is directly activated by diacylglycerol (DAG), cause a particularly aggressive form of FSGS. Angiotensin II, acting through its AT1 receptor, plays a critical role in generation of proteinuria and progression of kidney injury in a number of kidney diseases, including FSGS. Mounting evidence suggest the central role of TRPC6 and perhaps other TRPC channels in the pathogenesis of FSGS as well as of acquired forms of proteinuria such as diabetic nephropathy or hypertension. Identification of signaling pathways downstream of TRPC6 may provide novel targets for the treatment of proteinuria and prevent progression of podocyte injury.
authors.affiliation: Department of Pediatrics, Medical Faculty, University of Debrecen , Debrecen , Hungary.
authors.forename: T
authors.initials: T
authors.lastname: Szabó
authors.affiliation: DE-MTA "Lendület" Cellular Physiology Research Group, Department of Physiology, Medical Faculty, University of Debrecen , Debrecen , Hungary.
authors.forename: L
authors.initials: L
authors.lastname: Ambrus
authors.affiliation: DE-MTA "Lendület" Cellular Physiology Research Group, Department of Physiology, Medical Faculty, University of Debrecen , Debrecen , Hungary.
authors.forename: N
authors.initials: N
authors.lastname: Zákány
authors.affiliation: Department of Pediatrics, Medical Faculty, University of Debrecen , Debrecen , Hungary.
authors.forename: Gy
authors.initials: G
authors.lastname: Balla
authors.affiliation: DE-MTA "Lendület" Cellular Physiology Research Group, Department of Physiology, Medical Faculty, University of Debrecen , Debrecen , Hungary.
authors.forename: T
authors.initials: T
authors.lastname: Bíró
mesh_terms: D000818:Animals; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D005919:Glomerular Filtration Rate; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D009154:Mutation; D010641:Phenotype; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D011507:Proteinuria / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D000074287:TRPC6 Cation Channel
chemical_list: D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human
keywords: TRPC6; angiotensin II; diabetic nephropathy; focal segmental glomerulosclerosis (FSGS); podocyte; proteinuric disease