title: Transforming growth factor-β1 and diabetic nephropathy.
abstract: Transforming growth factor-β1 (TGF-β1) is established to be involved in the pathogenesis of diabetic nephropathy. The diabetic milieu enhances oxidative stress and induces the expression of TGF-β1. TGF-β1 promotes cell hypertrophy and extracellular matrix accumulation in the mesangium, which decreases glomerular filtration rate and leads to chronic renal failure. Recently, TGF-β1 has been demonstrated to regulate urinary albumin excretion by both increasing glomerular permeability and decreasing reabsorption in the proximal tubules. TGF-β1 also increases urinary excretion of water, electrolytes and glucose by suppressing tubular reabsorption in both normal and diabetic conditions. Although TGF-β1 exerts hypertrophic and fibrogenic effects in diabetic nephropathy, whether suppression of the function of TGF-β1 can be an option to prevent or treat the complication is still controversial. This is partly because adrenal production of mineralocorticoids could be augmented by the suppression of TGF-β1. However, differentiating the molecular mechanisms for glomerulosclerosis from those for the suppression of the effects of mineralocorticoids by TGF-β1 may assist in developing novel therapeutic strategies for diabetic nephropathy. In this review, we discuss recent findings on the role of TGF-β1 in diabetic nephropathy.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Albert S
authors.initials: AS
authors.lastname: Chang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Catherine K
authors.initials: CK
authors.lastname: Hathaway
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Oliver
authors.initials: O
authors.lastname: Smithies
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina mkakoki@med.unc.edu.
authors.forename: Masao
authors.initials: M
authors.lastname: Kakoki
mesh_terms: D000818:Animals; D003928:Diabetic Nephropathies / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D051269:Sodium-Glucose Transporter 1; D051297:Sodium-Glucose Transporter 2; D053773:Transforming Growth Factor beta1
keywords: megalin; nephrin; podocyte; proximal tubule; sodium-glucose cotransporter