Amphiregulin attenuates bleomycin-induced pneumopathy in mice
Amphiregulin attenuates bleomycin-induced pneumopathy in mice
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DOI：
10.1152/ajplung.90576.2008
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发表时间：
2010-02-01
影响因子：
4.9
通讯作者：
Nakanishi, Yoichi
中科院分区：
文献类型：
--
作者：
Fukumoto, Jutaro;Harada, Chika;Nakanishi, Yoichi
Fukumoto J，Harada C，Kawaguchi T，Suetsugu S，Maeyama T，Inoshima I，Hamada N，Kuwano K，Nakanishi Y。两性调节素减轻博莱霉素诱导的小鼠肺炎。Am J Physiol肺细胞分子Physiol 298：L131-L138,2010。首次发表于2009年11月13日；DOI：10.1152/ajpeng.90576.2008。-两亲调节素，一种表皮生长因子受体(EGFR)配体，对各种器官的上皮发育是必不可少的。最近的一份报告表明，在肝损伤模型中，两亲调节素起到了保护因素的作用。目前对双调节蛋白在肺损伤和肺纤维化中的作用知之甚少。本研究的目的是探讨两用调节素在博莱霉素性肺病小鼠模型中的作用。C57BL/6小鼠气管内注射盐酸博莱霉素溶液。分别于注射博莱霉素后第6、8、10、12天腹腔注射重组人两用调节素。采用TdT介导的dUTP缺口末端标记法(TUNEL)对肺组织进行组织学和生化分级，并计数肺组织中的凋亡细胞数。通过Western blotting分析和免疫组织化学方法检测肺组织中EGFR下游的存活信号，即磷酸化Akt和磷酸化Erk。博莱霉素组小鼠肺组织中内源性双调节素表达增加。给予重组双调蛋白可提高小鼠存活率，抑制肺组织炎症和纤维化程度，减少TUNEL阳性细胞数。双调蛋白可增强肺上皮细胞Akt和Erk的活性。双调蛋白可能通过激活存活信号在博莱霉素诱导的小鼠肺炎中起到保护作用。给药可能是一种新的抗肺损伤和纤维化的治疗策略。
Fukumoto J, Harada C, Kawaguchi T, Suetsugu S, Maeyama T, Inoshima I, Hamada N, Kuwano K, Nakanishi Y. Amphiregulin attenuates bleomycin-induced pneumopathy in mice. Am J Physiol Lung Cell Mol Physiol 298: L131-L138, 2010. First published November 13, 2009; doi: 10.1152/ajplung.90576.2008.-Amphiregulin, an EGF receptor (EGFR) ligand, is essential for epithelial development in various organs. A recent report suggested that amphiregulin acts as a protective factor in a liver injury model. Little is known about the roles of amphiregulin in lung injury and pulmonary fibrosis. The purpose of the present study was to investigate the role of amphiregulin in an experimental model of bleomycin-induced pneumopathy in mice. C57BL/6 mice were administered a bleomycin hydrochloride solution intratracheally. Recombinant human amphiregulin was injected intraperitoneally at 6, 8, 10, and 12 days after the bleomycin instillation. The grades of inflammation and fibrosis were assessed histologically and biochemically, and the numbers of apoptotic cells were counted after TdT-mediated dUTP nick end labeling (TUNEL) staining in the lung tissues. We also examined downstream survival signals of EGFR, namely phosphorylated Akt and phosphorylated Erk, in lung tissues by Western blotting analysis and immunohistochemistry. Expression of intrinsic amphiregulin was increased in murine lung tissues after bleomycin instillation. Administration of recombinant amphiregulin improved the survival rate and suppressed the degrees of inflammation and fibrosis and the number of TUNEL-positive cells in lung tissues. Amphiregulin treatment enhanced the activation of Akt and Erk in lung epithelial cells. Amphiregulin may play a protective role in bleomycin-induced pneumopathy in mice, probably through the activation of survival signals. Administration of amphiregulin may be a novel therapeutic strategy against lung injury and fibrosis.