The normal bladder has the ability to accommodate to large fluid volume changes without untoward pressure changes. Retention of this crucial function requires, among other variables, the maintenance of a complex extracellular matrix in both the mucosa and muscular detrusor layers. However, relatively little is known concerning the detailed molecular characteristics of this matrix either during development of the bladder or in disease situations. This proposal focuses on one of the major fibrous components of the bladder extracellular matrix, the elastic fiber, because of its central importance in normal function and because one of the cardinal features of a number of pathological conditions affecting the bladder is a loss of compliance and elastic recoil.
The specific aims of the proposal are to: (1) relate the molecular composition and temporal sequence of expression of components of the elastic fiber to the elastic properties of the developing bladder, (2) analyze the synthesis of components of the elastic fiber by cultured bladder smooth muscle cells, fibroblasts and urothelial cells, (3) determine the spatial distribution of elastic fiber components in the developing bladder. In order to achieve these aims, this proposal will apply rapidly accumulating new information concerning the identification and characterization of the proteins composing the elastic fiber and utilize state of the art molecular biologic, biochemical, immunologic, and ultrastructural analytical techniques. The bladders and cultured cells of male and female human and bovine fetuses of representative developmental ages will be analyzed. The results of these studies will shed light on extracellular matrix structure/function relationships in the bladder and identify specific proteins which may be involved in loss of the important property of elasticity.
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