Basic scienceCME articleTransforming growth factor-beta1–induced hypertrophy and matrix expression in human bladder smooth muscle cells
Section snippets
Material and methods
Smooth muscle cells were isolated from human bladder tissue removed during surgery for ureteral reimplantation with appropriate institutional approvals, as previously described.14 Cells were propagated in 45% Dulbecco’s minimal essential medium, 45% Hams-F12, 10% fetal bovine serum (FBS), 15 mmol/L N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid, penicillin/streptomycin, and amphotericin B in a humidified atmosphere of 5% CO2 in air and utilized from population doubling levels 2 to 8.
Cells
Hypertrophy and Hyperplasia
Bladder SMCs were treated with increasing concentrations of TGF-beta1, and total cell number was determined daily for 6 days. Smooth muscle cell proliferative response was refractory to all concentrations of TGF-beta1. No SMC hyperplasia response to increasing concentrations of TGF-beta1 was detected (data not shown). In contrast, TGF-beta1–treated SMCs became hypertrophic (30%–40% size increase) compared with nontreated control SMCs (Table I).
Collagen Protein Expression
Confluent detrusor SMC cultures were incubated in
Comment
These in vitro studies were carried out to determine whether bladder SMCs could respond to the profibrotic cytokine TGF-beta1 and whether the response could mimic in vivo conditions of hyperplasia/hypertrophy and altered collagen expression in obstructed bladders. Bladder SMCs did not show a proliferative response to TGF-beta1, similar to other cell types—vascular SMCs, mesangial cells, and also urothelial cells, in which TGF-beta1 can promote development of a differentiated urothelial layer in
Conclusions
Human bladder smooth muscle cells mediate both a hypertrophic and fibrotic response upon TGF-beta1 stimulation, which results in significant changes in the physiologic properties of the bladder.
Acknowledgment
To Z.Z. Tian for his technical assistance.
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Supported by U.S. Public Health Service grant DK-48215 (P.S.H.).