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Publication Date - 12/3/1999

21. NIH/NIDDK/NEI/NIDCR/NINDS & NHLBI - The Role of Growth Factors in the Development of Diabetes Complications

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Eye Institute (NEI), National Institute for Dental and Craniofacial Research (NIDCR), the National Institute of Neurological Disorders and Stroke (NINDS), and the National Heart, Lung, and Blood Institute (NHLBI) invite investigator-initiated research grant applications to study the role of growth factors in the etiology and pathogenesis of the micro- and macrovascular complications of diabetes. This program announcement (PA) is intended to stimulate the application of new molecular technologies in a systematic examination of the pathophysiologic role of growth factors in diabetic complications.

Studies strongly suggest a role for vascular endothelial growth factor (VEGF) in the pathogenesis of diabetic proliferative retinopathy. VEGF levels are increased in the vitreous of animals and humans with diabetic retinopathy, and agents which antagonize VEGF will suppress neovascularization of the retina. Although the available data indicate that VEGF is likely to play a critical role in the pathogenesis of diabetic retinopathy, its exact mechanism at the molecular level is not understood. Studies are needed to understand not only the cascade of events triggered by VEGF, but how hyperglycemia leads to VEGF upregulation.

New technologies, including the use of genetic knockouts, transgenic animals and chip array technology, provide powerful tools for studying the expression of growth factors during the development of the micro-macrovascular complications of diabetes, and for determining the molecular basis for their actions. Appropriate topics for investigation would include, but are not limited to, the following studies:

• to evaluate the tissue and/or cell specific expression of various growth factors during the development of complications, including a temporal analysis;
• to determine if activation or release of growth factors by matrix proteases is altered in diabetes;
• to determine what genes are up- or down-regulated by altered growth factor expressions;
• to determine if growth factor signaling pathways are altered in diabetic complications;
• to determine how hyperglycemic alters growth factor expression or action;
• to determine how other metabolic abnormalities associated with complications interact with alterations in growth factor expression and/or action;
• to test the role of growth factors in the pathogenesis of diabetic complications using animal models (including the use of knockout or transgenic animals).

The support mechanisms for this PA will be the NIH research project grant (RO1) and exploratory/development research grant (R21), which is intended to provide initial support for new investigators; allow exploration or possible innovative new directions for established investigators; and stimulate investigators from other areas to lend their expertise to research within the scope of this solicitation. R21 grants must limit their request to $100,000 direct costs per year and are limited to two years. Available funds are $2 million per year for three years when the PA terminates, October 1, 2002.

Applications are due at the NIH Center for Scientific Research on or before FEBRUARY 1, JUNE 1, or OCTOBER 1, 2000.

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