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mTOR、ZEB1、ROCK1在肺纤维化患者肺组织中的表达的临床意义

Clinical significance of mTOR, ZEB1, ROCK1 expression in lung tissues of pulmonary fibrosis patients.

作者信息

Park Jong Sun, Park Hyo Jin, Park Young Sik, Lee Sang-Min, Yim Jae-Joon, Yoo Chul-Gyu, Han Sung Koo, Kim Young Whan

机构信息

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea.

出版信息

BMC Pulm Med. 2014 Oct 31;14:168. doi: 10.1186/1471-2466-14-168.

Abstract

BACKGROUND

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown causes. Three proteins (mammalian target of rapamycin, mTOR; zinc finger E-box-binding homeobox 1, ZEB1; Rho-associated, coiled-coil containing protein kinase 1, ROCK1) may be related to pulmonary fibrosis. However, they have not been assessed in human pulmonary fibrosis. We assessed the clinical significance of mTOR, ZEB1, and ROCK1 expression in human pulmonary fibrosis of usual interstitial pneumonia (UIP) pattern.

METHODS

The mTOR, ZEB1, and ROCK1 expression was evaluated by immunohistochemical staining of 30 surgical lung biopsy tissues from 26 IPF and 4 UIP pattern connective tissue disease related interstitial lung disease (CTD-ILD) patients. The expression scores correlated with the clinical features.

RESULTS

The mTOR, ZEB1 and ROCK1 mainly expressed in alveolar epithelial cells of UIP lungs. The histological fibrosis scores and lung function decline in the strong mTOR expression group were higher than those in the weak and intermediate expression group. Patients with positive ZEB1 expression had higher fibrosis scores and greater decline in carbon monoxide diffusion capacity (DLCO) than patients with negative ZEB1 expression. Patients with positive mTOR or ZEB1 expression had poorer prognosis than that of patients with negative mTOR or ZEB1 expression, although it was not statistically significant. ROCK1 was not associated with the studied clinicopathological features.

CONCLUSIONS

The mTOR and ZEB1 expression in pulmonary fibrosis patients significantly correlated with the fibrosis score and lung function decline, indicating that it may be related to the prognosis of pulmonary fibrosis. Further studies involving large numbers of homogeneous IPF patients are warranted.

摘要

背景

特发性肺纤维化(IPF)是一种病因不明的致命性肺部疾病。三种蛋白(雷帕霉素靶蛋白,mTOR;锌指E盒结合同源框蛋白1,ZEB1;Rho相关卷曲螺旋蛋白激酶1,ROCK1)可能与肺纤维化有关。然而,它们尚未在人类肺纤维化中进行评估。我们评估了mTOR、ZEB1和ROCK1表达在普通型间质性肺炎(UIP)模式的人类肺纤维化中的临床意义。

方法

通过免疫组织化学染色评估26例IPF患者和4例UIP模式结缔组织病相关间质性肺病(CTD-ILD)患者的30份手术肺活检组织中mTOR、ZEB1和ROCK1的表达。表达评分与临床特征相关。

结果

mTOR、ZEB1和ROCK1主要在UIP肺的肺泡上皮细胞中表达。mTOR强表达组的组织学纤维化评分和肺功能下降高于弱表达组和中等表达组。ZEB1表达阳性的患者比ZEB1表达阴性的患者具有更高的纤维化评分和更大的一氧化碳弥散量(DLCO)下降。mTOR或ZEB1表达阳性的患者比mTOR或ZEB1表达阴性的患者预后更差,尽管差异无统计学意义。ROCK1与所研究的临床病理特征无关。

结论

肺纤维化患者中mTOR和ZEB1的表达与纤维化评分和肺功能下降显著相关,表明其可能与肺纤维化的预后有关。有必要对大量同质的IPF患者进行进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9fe/4233073/f13678a4b19e/12890_2013_610_Fig1_HTML.jpg

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