TY - JOUR
T1 - The decision to undergo DNA or protein synthesis is determined by the degree of mechanical deformation in human bladder muscle cells
AU - Orsola, Anna
AU - Adam, Rosalyn M.
AU - Peters, Craig A
AU - Freeman, Michael R.
N1 - Funding Information:
This study was supported by grants from the National Institutes of Health (R01 DK57691 and R01 DK55086).
PY - 2002
Y1 - 2002
N2 - Objectives. 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.
AB - Objectives. 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.
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U2 - 10.1016/S0090-4295(01)01648-X
DO - 10.1016/S0090-4295(01)01648-X
M3 - Article
C2 - 11992928
AN - SCOPUS:0036242865
SN - 0090-4295
VL - 59
SP - 779
EP - 783
JO - Urology
JF - Urology
IS - 5
ER -