The decision to undergo DNA or protein synthesis is determined by the degree of mechanical deformation in human bladder muscle cells.
OBJECTIVE
To investigate the effect of varying levels of mechanical deformation (cyclic stretch-relaxation) on protein and DNA synthesis rates in human bladder smooth muscle cells (SMCs). Cells in the bladder wall respond to outlet obstruction by increasing rates of protein synthesis ("hypertrophy") and/or DNA synthesis ("hyperplasia"); however, it is not established how these distinct processes are initiated.


METHODS
Primary cultures of human bladder SMCs were generated and maintained according to published methods. Cells were plated on type I collagen-coated elastomer-bottomed plates and subjected to cyclical stretch-relaxation (0.1 Hz) at 6%, 12%, and 20% elongation using a computer-controlled stretch-inducing device. DNA and protein synthesis rates were determined by uptake of radiolabeled thymidine and leucine, respectively. Nonstretched cells served as controls.


RESULTS
Mechanical stretch stimulated DNA synthesis in a dose and time-dependent manner with marked upregulation (4.5-fold) in response to 20% elongation. Mechanical deformation also elicited changes in protein synthesis in bladder SMCs. However, in contrast to the DNA synthesis pattern, leucine uptake over time was stimulated at 6% and 12% elongation, and no protein synthesis response was seen at 20% elongation.


CONCLUSIONS
Our findings suggest that stretch, in isolation from other potential mediators such as pressure or hypoxia, can induce either a hyperplastic or hypertrophic response in bladder SMCs and that the cells' response is dependent on the intensity of the stretch stimulus. These observations may be relevant to the process of in vivo tissue remodeling stimulated by bladder distension or contractile dysfunction.
Orsola
Anna
A
Urologic Laboratory, Department of Urology, Children's Hospital Boston and Department of Surgery, Harvard Medical School, Boston, Massachusetts 02115, USA.
Adam
Rosalyn M
RM
Peters
Craig A
CA
Freeman
Michael R
MR
D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism; D006984:Hypertrophy / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis*; D009130:Muscle, Smooth / Q000378:metabolism* / Q000473:pathology; D001743:Urinary Bladder / Q000378:metabolism* / Q000473:pathology
D009124:Muscle Proteins; D004247:DNA; D007930:Leucine