SP-C AND SURFACTANT HOMEOSTASIS

$177,876P01FY2000HLNIH

Children'S Hospital Med Ctr (Cincinnati), Cincinnati OH

Investigators

Linked publications & trials

Paper 25932959 Paper 20676040 Paper 20659319 Paper 20622029 Paper 19824815 Paper 19815549 Paper 19497999 Paper 19479035 Paper 19423771 Paper 19304906 Paper 19244201 Paper 19202005 Paper 19188657 Paper 19131640 Paper 19033457 Paper 18757315 Paper 18643778 Paper 18635891 Paper 18599506 Paper 18566429 Paper 18467707 Paper 18424623 Paper 18400946 Paper 18369093 Paper 18256198 Paper 18096869 Paper 18070348 Paper 17921358 Paper 17890326 Paper 17496152 Paper 17468132 Paper 17237346 Paper 17142160 Paper 16982851 Paper 16785550 Paper 16632521 Paper 16467360 Paper 16449190 Paper 16391428 Paper 16251411 Paper 16239640 Paper 16024721 Paper 15985750 Paper 15567715 Paper 15090366 Paper 15049696 Paper 15016617 Paper 14970209 Paper 14702106 Paper 14525980 Paper 12909592 Paper 12847272 Paper 12639841 Paper 12595595 Paper 12594064 Paper 12519727 Paper 12501227 Paper 12444140 Paper 12243725 Paper 12133857 Paper 12114208 Paper 12114186 Paper 12015304 Paper 11967276 Paper 11956209 Paper 11901176 Paper 11839553 Paper 11796696 Paper 11796659 Paper 11751207 Paper 11717240 Paper 11698462 Paper 11570159 Paper 11530131 Paper 11504713 Paper 11504698 Paper 11390505 Paper 11369537 Paper 11350807 Paper 11344267 Paper 11278637 Paper 11251302 Paper 11238009 Paper 11159019 Paper 11053018 Paper 11034401 Paper 10956621 Paper 10956619 Paper 10835321 Paper 10645893

Abstract

Although SP-C is the first surfactant component to appear during lung development, the function of SP-C is the least understood of the surfactant proteins. Several lines of evidence strongly support the hypothesis that SP-C is important for surfactant function and turnover: Replacement surfactants with recombinant SP-C as the sole protein component have the functional properties of natural surfactant in vitro and in vivo: and, most importantly, several term human infants with normal levels of SP-A and SP-B but undetectable SP-C protein rapidly developed severe RDS and ultimately succumbed to the disease. The overall goal of this project is to assess the role of SP-C in surfactant homeostasis. Intracellular trafficking, (specific aim 1) and secretion (specific aim 2) of SP-C will be characterized in isolated Type II epithelial cells. The role of SP-C in surfactant homeostasis will be assessed by characterizing the pathophysiology associated with expression of mutated or deleted SP-C constructs in vivo (specific aims 3 and 4). SP-C constructs will be expressed in Type II cells of SP-C knockout mice in order to achieve expression of the human transgene in a null background. The effect of transgene expression of the human transgene in a null background. The effect of transgene expression on lung structure and function will be assessed by biochemical, morphological and physiological analyses of the surfactant system in fetal and postnatal offspring. Transgenic mouse models will be generated to study the importance of acylation for mature SP-C function (specific aim 3) and the structural basis for optimal biologic activity of the mature peptide (specific aim 4). The experimental approach will permit characterization of the function of SP-C in the context of the whole animal as well as the isolated Type II cell and facilitate identification of its role in surfactant homeostasis.

View original record on NIH RePORTER →