Abstract
Bladder growth and development require continuous mechanical stimuli; however, abnormal mechanical conditions caused by partial bladder outlet obstruction (PBOO) result in detrusor smooth muscle hypertrophy and extracellular matrix accumulation. Our previous study demonstrated that PBOO induced an increase in monocyte chemotactic protein-1 (MCP-1) expression. To extensively illustrate whether and how MCP-1 participates in the remodeling of PBOO, we assess the pivotal effect of MCP-1 and its specific receptor chemokine (C-C motif) receptor 2 (CCR2) on the proliferation and contraction of human bladder smooth muscle cells (hBSMCs) under pathological hydrostatic pressure (HP). HP markedly promoted hBSMC proliferation and enhanced cell contraction along with the increase in MCP-1 expression. Recombinant human MCP-1 (rhMCP-1) enhanced HP-induced hBSMC proliferation and contraction. CCR2 antagonists and MCP-1 silencing reversed HP-induced proliferation and contraction. In addition, MCP-1-induced protein 1 (MCPIP1) silencing attenuated the contraction, but not the proliferation, induced by HP, whereas serum-glucocorticoid regulated kinase 1 (SGK1) silencing prevented the rhMCP-1-induced proliferation of hBSMCs under HP. Decrease of reactive oxygen species (ROS) level downregulated MCP-1 expression; in turn, rhMCP-1 promoted the generation of ROS. In conclusion, we demonstrated that pathological HP-promoted hBSMC proliferation was mainly regulated by the MCP-1/CCR2- SGK1 pathway and hBSMCs contraction was mainly moderated by the MCP-1/CCR2 -MCPIP1 pathway. [Figure: see text].