Hepatocyte growth factor prevents multiple organ injuries in endotoxemic mice through a heme oxygenase-1-dependent mechanism
Hepatocyte growth factor prevents multiple organ injuries in endotoxemic mice through a heme oxygenase-1-dependent mechanism
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DOI：
10.1016/j.bbrc.2009.01.080
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发表时间：
2009-03-06
影响因子：
3.1
通讯作者：
Nakamura, Toshikazu
中科院分区：
文献类型：
--
作者：
Kamimoto, Miyuki;Mizuno, Shinya;Nakamura, Toshikazu
急性肾功能衰竭(ARF)和急性呼吸窘迫综合征(ARDS)在脓毒症中仍然是致命性疾病，而血红素氧合酶-1(HO-1)可诱导宿主对脓毒症的防御反应。在此，我们提供了肝细胞生长因子(HGF)通过增强HO-1的诱导来预防ARF和ARDS的证据。脂多糖(LPS)处理的小鼠表现出与脓毒症患者相似的肾和肺损伤，而HGF增强了肾小管细胞和肺巨噬细胞中HO-1的诱导。结果表明，HGF可阻断脓毒症小鼠ARF和ARDS的发病。值得注意的是。HO-1抑制剂(SnPP)可减弱HGF对内毒素诱导的器官损伤的保护作用。此外，SnPP可恢复HGF对IL-1β和IL-18上调的抑制作用。这是首次报道“生长因子疗法”成功地抑制了内毒素血症中的ARDS和ARF，部分是通过抑制HO-1依赖的高细胞分裂素血症。(C)2009 Elsevier Inc.保留所有比赛。
Acute renal failure (ARF) and acute respiratory distress syndrome (ARDS) are still lethal diseases during sepsis, whereas heme oxygenase-1 (HO-1) elicits a host defense response to sepsis. Herein, we provide evidence that hepatocyte growth factor (HGF) prevents ARF and ARDS via enhanced induction of HO-1. Lipopolysaccharide (LPS)-treated mice manifested renal and pulmonary injuries similar to those observed in septic patients, while HGF enhanced the HO-1 induction in renal tubular cells and in lung macrophages. As a result, onsets of ARF and ARDS were blocked by HGF in septic mice. Notably. an HO-1 inhibitor (SnPP) diminished the protective effects of HGF on LPS-induced organ injuries. Furthermore, the inhibitory effect of HGF on up-regulation of interleukin-1 beta and interleukin-18 was largely restored by SnPP. This is the first report showing that "growth factor therapy" Successfully inhibits both ARDS and ARF during endotoxemia, partially via HO-1-dependent suppression of hyper-cytokinemia. (c) 2009 Elsevier Inc. All Fights reserved.