title: The role of metabolic and haemodynamic factors in podocyte injury in diabetes.
abstract: Podocyte loss is a common feature in human diabetes as well as in experimental diabetes in rodents. Almost all components of the diabetic milieu lead to serious podocyte stress, driving the cells towards cell cycle arrest and hypertrophy, detachment and apoptosis. Common pathway components induced by high glucose and advanced glycation end-products are reactive oxygen species, cyclin-dependent kinases (p27(Kip1)) and transforming growth factor-beta. In addition, mechanical stresses by stretch or shear forces, insulin deficiency or insulin resistance are independent components resulting in podocyte apoptosis and detachment. In this review, we discuss the common pathways leading to podocyte death as well as novel pathways and concepts of podocyte dedifferentiation and detachment that influence the progression of diabetic glomerulopathy.
authors.affiliation: Division of Nephrology, Department of Medicine, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Stieger
authors.forename: Kirstin
authors.initials: K
authors.lastname: Worthmann
authors.forename: Mario
authors.initials: M
authors.lastname: Schiffer
mesh_terms: D000199:Actins / Q000502:physiology; D017209:Apoptosis; D018925:Chemokines / Q000502:physiology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D016207:Cytokines / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance; D050199:Podocytes / Q000378:metabolism / Q000473:pathology*; D013314:Stress, Mechanical; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000199:Actins; D018925:Chemokines; D016207:Cytokines; D017127:Glycation End Products, Advanced; D007328:Insulin; D016212:Transforming Growth Factor beta; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005947:Glucose