The p53-Mdm2 association in epithelial cells in idiopathic pulmonary fibrosis and non-specific interstitial pneumonia
The p53-Mdm2 association in epithelial cells in idiopathic pulmonary fibrosis and non-specific interstitial pneumonia
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DOI：
10.1136/jcp.2004.022632
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发表时间：
2005-06-01
影响因子：
3.4
通讯作者：
Nakanishi, Y
中科院分区：
文献类型：
--
作者：
Nakashima, N;Kuwano, K;Nakanishi, Y
背景：野生型p53在细胞对各种应激的反应中增加。目的：探讨Mdm 2介导的p53蛋白泛素化与特发性肺纤维化（IPF）肺上皮细胞凋亡的关系。对通过肺活检获得的IPF和非特异性间质性肺炎患者的肺样本进行免疫组织化学和蛋白质印迹分析（结果：与正常肺实质相比，IPF和NSIP患者的上皮细胞中p53、磷酸化p53、Mdm 2、p21和Bax的表达上调。与NSIP相比，IPF中除p21外，这些因子的表达均显著增加。凋亡细胞数、p53和Bax阳性细胞数均较对照组增多。与NSIP和对照组相比，IPF中与Mdm 2缀合的p53减少。结论：与p53介导的细胞凋亡相关的信号分子可能参与了上皮细胞凋亡，p53 -Mdm 2结合的减弱和p53降解的减弱可能参与了IPF上皮细胞凋亡。与NSIP相比，IPF中上皮细胞凋亡增加可能导致预后不良。
Background: Wild-type p53 is increased during cellular responses to various stresses. Mdm2, which is induced by p53, regulates p53 protein concentrations through the ubiquitin - proteasome pathway.Aim: To investigate whether the Mdm2 mediated ubiquitination of p53 is associated with epithelial cell apoptosis in idiopathic pulmonary fibrosis (IPF).Methods: Immunohistochemistry and western blot analysis were carried out on lung samples obtained by lung biopsy from patients with IPF and non-specific interstitial pneumonia (NSIP).Results: The expression of p53, phosphorylated p53, Mdm2, p21, and Bax was upregulated in epithelial cells from patients with IPF and NSIP compared with normal lung parenchyma. Except for p21, there was a significant increase in the expression of these factors in IPF compared with NSIP. In addition, the number of apoptotic cells and the number of p53 and Bax positive cells was increased compared with controls. p53 conjugated with Mdm2 was decreased in IPF compared with NSIP and controls. Ubiquitinated p53 was increased in both IPF and NSIP compared with controls.Conclusions: Signalling molecules associated with p53 mediated apoptosis may participate in epithelial cell apoptosis, and the attenuation of p53 - Mdm2 conjugation and of p53 degradation may be involved in the epithelial cell apoptosis seen in IPF. Augmented epithelial apoptosis in IPF may lead to the poor prognosis compared with NSIP.