Monocyte Chemotactic Protein-1 Regulates Proliferation and Contractility of Human Bladder Smooth Muscle Cells Under Hydrostatic Pressure
Monocyte Chemotactic Protein-1 Regulates Proliferation and Contractility of Human Bladder Smooth Muscle Cells Under Hydrostatic Pressure
复制标题
单核细胞趋化蛋白-1 调节静水压下人膀胱平滑肌细胞的增殖和收缩性
DOI：
10.1089/jir.2019.0186
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发表时间：
2020
影响因子：
2.3
通讯作者：
Wang Kunjie
中科院分区：
文献类型：
--
作者：
Chen Guo;Jin Xi;Gao Xiaoshuai;Ai Jianzhong;Luo Deyi;Zhou Liang;Xiao Kaiwen;Li Zirui;Li Hong;Wang Kunjie
膀胱的生长和发育需要持续的机械刺激;然而，由部分膀胱出口梗阻（PBOO）引起的异常机械条件导致逼尿肌平滑肌肥大和细胞外基质积聚。我们以前的研究表明，PBOO诱导单核细胞趋化蛋白-1（MCP-1）的表达增加。为了更广泛地阐明MCP-1是否以及如何参与PBOO的重塑，我们评估了MCP-1及其特异性受体趋化因子（C-C基序）受体2（CCR 2）对病理静水压力（HP）下人膀胱平滑肌细胞（hBSMCs）增殖和收缩的关键作用。HP可明显促进hBSMC增殖，并随着MCP-1表达的增加而沿着增强细胞收缩。重组人MCP-1（rhMCP-1）增强HP诱导的hBSMC增殖和收缩。CCR 2拮抗剂和MCP-1沉默逆转HP诱导的增殖和收缩。此外，MCP-1诱导的蛋白1（MCPIP 1）沉默减弱了HP诱导的收缩，但不抑制HP诱导的增殖，而血清糖皮质激素调节激酶1（SGK 1）沉默则阻止了HP诱导的rhMCP-1诱导的hBSMCs增殖。活性氧（reactive oxygen species，ROS）水平的降低可下调MCP-1的表达，而rhMCP-1可促进ROS的产生。综上所述，我们证明了病理性HP促进的hBSMC增殖主要由MCP-1/CCR 2-SGK 1通路调节，hBSMC收缩主要由MCP-1/CCR 2-MCPIP 1通路调节。
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.