The long term goal of this application is to understand the mechanism by which bladder smooth muscle cells respond to mechanical signals which are a part of their immediate in vivo environment. An apparatus has been developed which permits the application of precise levels of biaxal deformation to cells in culture. The effects of this mechanical strain can be assessed morphologically, biochemically, and physiologically. It is hypothesized that stress induced by stretch or hydrostatic pressure alters bladder smooth muscle cells and that one result of this deformation is an alteration in connective tissue synthesis which causes the bladder to become less compliant.
The specific aims of this proposal are: (1) to set up an in vitro model using bladder smooth muscle cells and to mechanically deform these cells using stretch and or hydrostatic pressure; and (2) to determine if matrix synthesis by bladder smooth muscle cells is altered under strained and unstrained conditions.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Surgery, Anesthesiology and Trauma Study Section (SAT)
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University of Pennsylvania
Schools of Dentistry
United States
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Wei, Wenjie; Howard, Pamela S; Kogan, Barry et al. (2007) Altered extracellular matrix expression in the diverted fetal sheep bladder. J Urol 178:1104-7
Macarak, Edward J; Schulz, Jake; Zderic, Stephen A et al. (2006) Smooth muscle trans-membrane sarcoglycan complex in partial bladder outlet obstruction. Histochem Cell Biol 126:71-82
He, Yuling; Macarak, Edward J; Korostoff, Jonathan M et al. (2004) Compression and tension: differential effects on matrix accumulation by periodontal ligament fibroblasts in vitro. Connect Tissue Res 45:28-39
Kirsch, Andrew J; Macarak, Edward J; Chaqour, Brahim et al. (2003) Molecular response of the bladder to obstruction. Adv Exp Med Biol 539:195-216
Coplen, Douglas E; Macarak, Edward J; Howard, Pamela S (2003) Matrix synthesis by bladder smooth muscle cells is modulated by stretch frequency. In Vitro Cell Dev Biol Anim 39:157-62
Cavalcant-Adam, E A; Shapiro, I M; Composto, R J et al. (2002) RGD peptides immobilized on a mechanically deformable surface promote osteoblast differentiation. J Bone Miner Res 17:2130-40
Tamura, I; Rosenbloom, J; Macarak, E et al. (2001) Regulation of Cyr61 gene expression by mechanical stretch through multiple signaling pathways. Am J Physiol Cell Physiol 281:C1524-32
Billings, P C; Herrick, D J; Kucich, U et al. (2000) Extracellular matrix and nuclear localization of beta ig-h3 in human bladder smooth muscle and fibroblast cells. J Cell Biochem 79:261-73
Chaqour, B; Howard, P S; Richards, C F et al. (1999) Mechanical stretch induces platelet-activating factor receptor gene expression through the NF-kappaB transcription factor. J Mol Cell Cardiol 31:1345-55
Chang, S L; Howard, P S; Koo, H P et al. (1998) Role of type III collagen in bladder filling. Neurourol Urodyn 17:135-45

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