Pathogenic role of TGF-β in the progression of podocyte diseases.
In patients with progressive podocyte diseases, such as focal segmental glomerulosclerosis and membranous nephropathy, there is enhanced expression of transforming growth factor (TGF-β) in podocytes. Biomechanical strain in these diseases may cause overexpression of TGF-β and angiotensin II (Ang II) by podocytes. Oxidative stress induced by Ang II may activate the latent TGF-β. Increased TGF-β activity by podocytes may induce not only the thickening of the glomerular basement membrane (GBM), but also podocyte apoptosis and/or detachment from the GBM, initiating the development of glomerulosclerosis. Furthermore, mesangial matrix expansion frequently occurs in podocyte diseases in association with the development of glomerulosclerosis. This review examines open questions on the pathogenic role of TGF-β that links podocyte injury to GBM thickening, podocyte loss, mesangial matrix expansion and glomerulosclerosis in podocyte diseases. It also describes paracrine regulatory mechanisms of podocyte TGF-β on mesangial cells leading to increased matrix synthesis.
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea. hyunsoon@plaza.snu.ac.kr
Hyun Soon
HS
Lee
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D001696:Biomechanical Phenomena; D055513:Connective Tissue Growth Factor / Q000502:physiology; D030321:Denys-Drash Syndrome / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D050533:Glomerular Basement Membrane / Q000473:pathology / Q000503:physiopathology; D015433:Glomerulonephritis, Membranous / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D006977:Hypertension, Renal / Q000503:physiopathology; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D008954:Models, Biological; D019899:Paracrine Communication; D050199:Podocytes / Q000473:pathology* / Q000502:physiology*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
C526317:CCN2 protein, human; D016212:Transforming Growth Factor beta; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000804:Angiotensin II; D055513:Connective Tissue Growth Factor