The applicant proposes to test the hypothesis that Ca absorption is mostly mediated through the tight junction /intercellular space system, the paracellular conduit. The objectives are: 1) To demonstrate in vivo Ca absorption is mostly mediated through the paracellular conduit using an intact-rat model with unmanipulated intestinal tract. 2) To define qualitative and quantitative characteristics of paracellular Ca absorption using different segments of rat intestinal epithelium and cultured enterocyte monolayers. In the intact-rat model, in vivo Ca absorption will be measured in different segments of the intestine. The information from whole-animal studies will be complemented by in vitro transepithelial transport studies using natural epithelium from duodenum, jejunum, ileum, cecum, colon and monolayers of the IEC6, IEC18, T84 and Caco-2 cell lines. The third group of studies examines the role of tyrosine phosphorylation and calpain-mediated proteolysis of junctional proteins on cytoskeletal remodelling and changes in paracellular Ca absorption. The possibility that paracellular solute traffic can be augmented by not only changes in TJ permeability but also a """"""""widening"""""""" of the intercellular space through enterocyte contraction and retraction from its focal contacts and the basement membrane will be examined. In all studies, the possibility that vitamin D, lactose, and bile salts (taurodeoxycholic acid) exert their stimulatory influence on Ca absorption through the paracellular conduit will be addressed.
| Lee, David B N; Jamgotchian, Nora; Allen, Suni G et al. (2008) A lipid-protein hybrid model for tight junction. Am J Physiol Renal Physiol 295:F1601-12 |
| Lee, David B N; Huang, Edmund; Ward, Harry J (2006) Tight junction biology and kidney dysfunction. Am J Physiol Renal Physiol 290:F20-34 |
| Lee, David B N; Jamgotchian, Nora; Allen, Suni G et al. (2004) Annexin A2 heterotetramer: role in tight junction assembly. Am J Physiol Renal Physiol 287:F481-91 |
