Effect of cyclic hydrodynamic pressure‐induced proliferation of human bladder smooth muscle through Ras‐related C3 botulinum toxin substrate 1, mitogen‐activated protein kinase kinase 1/2 and extracellular regulated protein kinases 1/2

Objectives: To examine the role of Ras‐related C3 botulinum toxin substrate 1, mitogen‐activated protein kinase kinase 1/2 and extracellular regulated protein kinases 1/2 in the cyclic hydrodynamic pressure‐induced proliferation of human bladder smooth muscle cells. Methods: Human bladder smooth muscle cells were exposed to cyclic hydrodynamic pressures in vitro with defined parameters (static, 100 cmH₂O, 200 cmH₂O and 300 cmH₂O pressure) for 24 h. The proliferation of cells was assessed by flow cytometry. Ras‐related C3 botulinum toxin substrate 1, mitogen‐activated protein kinase kinase 1/2 and extracellular regulated protein kinases 1/2 messenger ribonucleic acid, and protein expression was analyzed by real‐time polymerase chain reaction and Western blot. Specificity of the Rac1 was determined with real‐time polymerase chain reaction and Western blot technique with small interfering ribonucleic acid transfection and Rac1 inhibitor (NSC23766). Results: The proliferation of human bladder smooth muscle cells was increased. Ras‐related C3 botulinum toxin substrate 1, mitogen‐activated protein kinase kinase 1/2 and extracellular regulated protein kinases 1/2 were activated by 200 and 300 cmH₂O cyclic hydrodynamic pressure compared with static and 100 cmH₂O pressure. The “knockdown” of activation of Rac1 using target small interfering ribonucleic acid transfection and Rac1 inhibitor (NSC23766) decreased proliferation of human bladder smooth muscle cells, and downregulated mitogen‐activated protein kinase kinase 1/2, extracellular regulated protein kinases 1/2. Conclusion: The Rac1 pathway is activated in mechanotransduction and regulation of human bladder smooth muscle cell proliferation in response to cyclic hydrodynamic pressure.