Grant: $605,250 - National Institutes of Health - Sep. 30, 2009
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Award Description: This is an application for a competitive supplement for grant 5R37DK33209-27, in response to NIH Notice Number (NOT-OD-09-058) entitled 'NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications . The original application and the subject of ongoing studies is focused on understanding of the function of novel key players in the systemic phosphate homeostasis and how they are affected by chronic inflammatory conditions, particularly as it relates to the metabolic bone disease, osteopenia and osteoporosis in patients with Inflammatory Bowel Diseases. This application for a competitive supplement is aimed at expanding the scope of our research to another key component related to bone health, calcium, and the effects and the mechanisms of action of inflammation and inflammatory mediators on intestinal and renal calcium handling. While it is commonsense that calcium deficiency may be one of the underlying factors in the IBD-associated bone loss, the mechanisms by which the Ca2+ absorptive and reabsorptive mechanisms are affected are largely unknown. We demonstrate preliminary data on the effects of acute and chronic colitis on the expression of key transport proteins involved in renal Ca2+ reabsorption, including the novel regulatory gene, Klotho. These results allow us to formulate a novel hypothesis about the mechanisms of Klotho-dependent and independent mechanisms of inhibition of the epithelial calcium channel function by inflammatory mediators in mouse models of IBD. In this supplemental application, we propose to invest additional resources into understanding the effects of colitis and inflammatory mediators on: (1) the functional capacity of the intestinal and renal Ca2+ transport mechanism; (2) intestinal expression of TRPV6; and (3) Klotho-dependent downregulation of renal TRPV5 and intestinal TRPV6 function. This supplemental funding mechanism will allow us to expand the scope of our focus to another key component of the systemic mineral homeostasis making our approaches more comprehensive. It will also fulfill the criteria for the ARRA, including job preservation and/or creation, and investment into scientific endeavors which will help us understand the increasingly acknowledged clinical problem, namely metabolic bone disease and bone loss in idiopathic chronic inflammatory conditions.
Project Description: As defined in the award description field.
Jobs Summary: N/A (Total jobs reported: 0)
Project Status: Not Started
This award's data was last updated on Sep. 30, 2009. Help expand these official descriptions using the wiki below.