title: Role of TGF-β in chronic kidney disease: an integration of tubular, glomerular and vascular effects.
abstract: Transforming growth factor beta (TGF-β) has been recognized as an important mediator in the genesis of chronic kidney diseases (CKD), which are characterized by the accumulation of extracellular matrix (ECM) components in the glomeruli (glomerular fibrosis, glomerulosclerosis) and the tubular interstitium (tubulointerstitial fibrosis). Glomerulosclerosis is a major cause of glomerular filtration rate reduction in CKD and all three major glomerular cell types (podocytes or visceral epithelial cells, mesangial cells and endothelial cells) participate in the fibrotic process. TGF-β induces (1) podocytopenia caused by podocyte apoptosis and detachment from the glomerular basement membrane; (2) mesangial expansion caused by mesangial cell hypertrophy, proliferation (and eventually apoptosis) and ECM synthesis; (3) endothelial to mesenchymal transition giving rise to glomerular myofibroblasts, a major source of ECM. TGF-β has been shown to mediate several key tubular pathological events during CKD progression, namely fibroblast proliferation, epithelial to mesenchymal transition, tubular and fibroblast ECM production and epithelial cell death leading to tubular cell deletion and interstitial fibrosis. In this review, we re-examine the mechanisms involved in glomerulosclerosis and tubulointerstitial fibrosis and the way that TGF-β participates in renal fibrosis, renal parenchyma degeneration and loss of function associated with CKD.
authors: Departamento de Fisiología y Farmacología, Unidad de Fisiopatología Renal y Cardiovascular, Universidad de Salamanca, Edificio Departamental S-20 Campus Miguel de Unamuno, 37007 Salamanca, Spain.
authors: Francisco J
authors: FJ
authors: López-Hernández
authors: Jose M
authors: JM
authors: López-Novoa
mesh_terms: D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000473:pathology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000473:pathology / Q000503:physiopathology; D007684:Kidney Tubules / Q000166:cytology / Q000473:pathology / Q000503:physiopathology; D050199:Podocytes / Q000473:pathology / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta