Liu C Y, Zhou L L, Cheng Q, Jiang S N, Sheng J, Sun J D, Zhao J Y
Department of Nephrology, Second Hospital of Dalian Medical University, Shahekou District, Dalian Liaoning Province, China.
Department of Nephrology, Second Hospital of Dalian Medical University, Shahekou District, Dalian Liaoning Province, China
Genet Mol Res. 2014 Jan 21;13(1):490-8. doi: 10.4238/2014.January.21.18.
Recent studies have found that bradykinin (BK) plays a role in delaying glomerulosclerosis, although the mechanism of this phenomenon remains unclear. Mesangial cell proliferation (MCP) and extracellular matrix (ECM) secretion are important mechanisms for glomerulosclerosis. This study investigated the impact of BK on the platelet-derived growth factor (PDGF)-induced proliferation of mesangial cells, and evaluated its correlations with the extracellular signal-related kinase (ERK) signaling pathway. The results showed that on its own, 10-1000 mg/L BK promoted MCP and ECM secretion and induced ERK phosphorylation. However, BK administration after PDGF pre-incubation inhibited PDGF-induced MCP, ECM secretion, and ERK phosphorylation. The BK B2 receptor-specific antagonist, HOE-140, and tyrosine phosphatase inhibitor (OV) effectively blocked the function of BK. In summary, these results demonstrated that BK has a bidirectional effect on MCP and ECM secretion: when used alone, it promoted effects on these phenomena, but these effects were inhibited when combined with PDGF. This suggests that the role of BK might be achieved through inhibiting activation of the PDGF-induced ERK1/2 pathway.
近期研究发现，缓激肽（BK）在延缓肾小球硬化中发挥作用，尽管这一现象的机制尚不清楚。系膜细胞增殖（MCP）和细胞外基质（ECM）分泌是肾小球硬化的重要机制。本研究调查了BK对血小板衍生生长因子（PDGF）诱导的系膜细胞增殖的影响，并评估其与细胞外信号调节激酶（ERK）信号通路的相关性。结果显示，单独使用时，10 - 1000 mg/L的BK促进MCP和ECM分泌并诱导ERK磷酸化。然而，在PDGF预孵育后给予BK则抑制了PDGF诱导的MCP、ECM分泌及ERK磷酸化。BK B2受体特异性拮抗剂HOE - 140和酪氨酸磷酸酶抑制剂（OV）有效阻断了BK的作用。总之，这些结果表明BK对MCP和ECM分泌具有双向作用：单独使用时，它促进这些现象，但与PDGF联合使用时这些作用受到抑制。这表明BK的作用可能是通过抑制PDGF诱导的ERK1/2通路的激活来实现的。
