The bladder is routinely subjected to mechanical stretch from filling cycles; however, abnormal bladder distention can result from pathological conditions such as bladder outlet obstruction. It has been suggested that abnormal mechanical environments in the bladder trigger cellular and molecular changes, such as smooth muscle cell hyperplasia or hypertrophy and alteration of the extracellular matrix (ECM). These cellular and ECM changes can, in turn, deteriorate the function of the bladder by decreasing the contractility and compliance of the tissue [1, 3, 5]. While the exact mechanisms that cause these changes in the bladder remain unknown, previous studies have demonstrated increases in DNA synthesis and expression of genes for HB-EGF and COX-2, in response to cyclic stretch in vitro [1, 2, 4]. Although these studies provided valuable information, two-dimensional culture of smooth muscle cells (SMCs) does not completely represent physiological conditions since the bladder cells in vivo exist as clusters surrounded by collagen sheath in a three-dimensional environment. The overall goal of our study, therefore, is to investigate, using 3-D cell cultures, the effects of sustained stretch, which is aimed to simulate chronic overdistension, on SMC function pertinent to bladder tissue remodeling observed under pathological conditions. In the present study, we examined the effects of cell-to-cell contact and of 3-D culture environment with or without constant tension on bladder SMC phenotypic marker expression.
展开▼
