In summary, metabolic, hemodynamic, and genetic factors are all important in the development and progression of
diabetic nephropathy (33). Recent studies using cell culture techniques and experimental animal models have provided important insight into the role of
hyperglycemia in this disease. The nature of the factors directly arising as a consequence of
hyperglycemia and the steps involved in
diabetic complications are not completely understood. The characteristic lesions of
diabetic nephropathy may be intimately related to the effects of high ambient
glucose on intracellular signaling events, various
growth factors/
cytokines, and nonenzymatic glycation of
proteins (36). The
growth factor TGF-beta has emerged as a key participant in the cascade of events which leads to kidney
sclerosis. Increased
TGF-beta expression in the kidney in
diabetes mellitus mediates the renal actions of high ambient
glucose to promote cellular
hypertrophy and stimulate extracellular matrix biosynthesis. Neutralizing the actions of
TGF-beta with highly specific
monoclonal antibodies or with application of antisense technology can effectively prevent the induction of the kidney lesions of diabetes in mice independent of any changes in
blood glucose levels. Such maneuvers are crucial for establishing proof-of-concept and Koch's postulates (17), but they are still far removed from clinical applicability. Nevertheless, it is hoped that further studies to elucidate the efficacy of novel interventions to intercept the activity of the renal
TGF-beta system will prove useful for effectively halting the progression of
diabetic nephropathy.