Nakashima N, Kuwano K, Maeyama T, Hagimoto N, Yoshimi M, Hamada N, Yamada M, Nakanishi Y
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Fukuoka 812-8582, Japan.
J Clin Pathol. 2005 Jun;58(6):583-9. doi: 10.1136/jcp.2004.022632.
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.
To investigate whether the Mdm2 mediated ubiquitination of p53 is associated with epithelial cell apoptosis in idiopathic pulmonary fibrosis (IPF).
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).
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.
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.
野生型p53在细胞对各种应激的反应过程中会增加。由p53诱导产生的Mdm2通过泛素-蛋白酶体途径调节p53蛋白浓度。
研究Mdm2介导的p53泛素化是否与特发性肺纤维化（IPF）中的上皮细胞凋亡有关。
对通过肺活检从IPF患者和非特异性间质性肺炎（NSIP）患者获取的肺样本进行免疫组织化学和蛋白质印迹分析。
与正常肺实质相比，IPF和NSIP患者上皮细胞中p53、磷酸化p53、Mdm2、p21和Bax的表达上调。与NSIP相比，除p21外，IPF中这些因子的表达显著增加。此外，与对照组相比，凋亡细胞数量以及p53和Bax阳性细胞数量增加。与NSIP和对照组相比，IPF中与Mdm2结合的p53减少。与对照组相比，IPF和NSIP中泛素化p53均增加。
与p53介导的凋亡相关的信号分子可能参与上皮细胞凋亡，p53-Mdm2结合及p53降解的减弱可能与IPF中所见的上皮细胞凋亡有关。与NSIP相比，IPF中上皮细胞凋亡增加可能导致预后不良。
