Mitogenic properties of endogenous and pharmacological doses of macrophage inflammatory protein-2 after 70% hepatectomy in the mouse
Mitogenic properties of endogenous and pharmacological doses of macrophage inflammatory protein-2 after 70% hepatectomy in the mouse
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DOI：
10.1016/s0002-9440(10)63684-x
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发表时间：
2003-08-01
影响因子：
6
通讯作者：
Colletti, L
中科院分区：
文献类型：
--
作者：
Ren, XD;Carpenter, A;Colletti, L
最近的研究表明，肝切除术后CXC趋化因子升高;阻断上皮细胞趋化因子ENA-78（一种CXC趋化因子）可延缓切除术后的肝再生。另外的研究表明，当其他疗法失败时，外源性巨噬细胞炎性蛋白（MIP）-2（另一种CXC趋化因子）在鼠对乙酰氨基酚毒性模型中具有治疗作用。目前的调查研究MIP-2的影响，在70%肝切除后的小鼠参与肝再生的细胞机制。通过5-溴-2 '-脱氧尿苷染色测量，70%肝切除术后给予外源性MIP-2显著增加肝细胞增殖。信号转导子和转录激活子-3（stat-3）也检测到更大的丰度，并持续在MIP-2治疗的小鼠肝细胞核提取物与对照小鼠肝切除术后。此外，MIP-2受体CXCR 2的抑制降低了部分肝切除术背景下的基线肝细胞增殖和stat-3表达。这些数据表明，MIP-2是重要的肝部分切除术后的肝细胞增殖和药理学MIP-2剂量肝损伤后加速肝再生。
Recent studies show CXC chemokine elevations after hepatic resection; blockade of epithelial neutrophilactivating protein (ENA-78), a CXC chemokine, retards hepatic regeneration after resection. Additional studies demonstrate that exogenous macrophage inflammatory protein (MIP)-2, another CXC chemokine, is therapeutic in a murine acetaminophen toxicity model when other therapies fail. The current investigations study MIP-2's effects on the cellular mechanisms involved in liver regeneration in mice after 70% hepatectomy. Administration of exogenous MIP-2 after 70% hepatectomy dramatically increased hepatocyte proliferation as measured by 5-bromo-2'deoxyuridine staining. Signal transducer and activator of transcription-3 (stat-3) was also detected in greater abundance and persisted in hepatic nuclear extracts from MIP-2-treated mice compared with control mice after hepatic resection. Further, inhibition of the MIP-2 receptor, CXCR2, decreased baseline hepatocyte proliferation and stat-3 expression in the setting of partial hepatectomy. These data show that MIP-2 is important for hepatocyte proliferation after partial hepatectomy and that pharmacological MIP-2 doses after hepatic injury accelerate hepatic regeneration.