Transforming growth factor-β1 and diabetic nephropathy

Transforming growth factor-beta 1 (TGF-beta 1) is established to be involved in the pathogenesis of diabetic nephropathy. The diabetic milieu enhances oxidative stress and induces the expression of TGF-beta 1. TGF-beta 1 promotes cell hypertrophy and extracellular matrix accumulation in the mesangium, which decreases glomerular filtration rate and leads to chronic renal failure. Recently, TGF-beta 1 has been demonstrated to regulate urinary albumin excretion by both increasing glomerular permeability and decreasing reabsorption in the proximal tubules. TGF-beta 1 also increases urinary excretion of water, electrolytes and glucose by suppressing tubular reabsorption in both normal and diabetic conditions. Although TGF-beta 1 exerts hypertrophic and fibrogenic effects in diabetic nephropathy, whether suppression of the function of TGF-beta 1 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-beta 1. However, differentiating the molecular mechanisms for glomerulosclerosis from those for the suppression of the effects of mineralocorticoids by TGF-beta 1 may assist in developing novel therapeutic strategies for diabetic nephropathy. In this review, we discuss recent findings on the role of TGF-beta 1 in diabetic nephropathy.