Transforming growth factor-β1 and diabetic nephropathy

• Published in: American journal of physiology. Renal physiology Vol. 310; no. 8; p. F689
• Main Authors: Chang, Albert S, Hathaway, Catherine K, Smithies, Oliver, Kakoki, Masao
• Format: Journal Article
• Language: English
• Published: United States 15-04-2016
• Subjects: Animals; Diabetic Nephropathies - metabolism; Humans; Kidney - metabolism; Oxidative Stress - physiology; Sodium-Glucose Transporter 1 - metabolism; Sodium-Glucose Transporter 2 - metabolism; Transforming Growth Factor beta1 - metabolism; sodium-glucose cotransporter; nephrin; proximal tubule; megalin; podocyte
• ISSN: 1522-1466
• DOI: 10.1152/ajprenal.00502.2015

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.