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血清和肺组织中几丁质酶样蛋白 YKL-40 在特发性肺纤维化患者中的高表达。

Increased expression of YKL-40, a chitinase-like protein, in serum and lung of patients with idiopathic pulmonary fibrosis.

机构信息

Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama Higashiku, Hamamatsu, Shizuoka 431-3192, Japan.

出版信息

Respir Med. 2010 Aug;104(8):1204-10. doi: 10.1016/j.rmed.2010.02.026. Epub 2010 Mar 27.

DOI:10.1016/j.rmed.2010.02.026
PMID:20347285
Abstract

BACKGROUND

YKL-40, a mammalian member of chitinase-like proteins, has been shown to play a role in pathological conditions leading to tissue remodeling and fibrosis. Recently, YKL-40 was found to be increased in severe asthma, suggesting that YKL-40 contributes to airway remodeling; however, no data are available about YKL-40 expression in idiopathic pulmonary fibrosis (IPF). The present study was conducted to investigate YKL-40 expression in the serum and lung of IPF patients, and to determine its clinical significance.

METHODS

Using an enzyme-linked immunosorbent assay, we measured YKL-40 levels in the serum of 63 IPF patients and in bronchoalveolar lavage fluid (BALF) of 18 IPF patients. YKL-40 levels were also assessed in the serum and BALF of healthy subjects. We further investigated the relationship between serum YKL-40 levels and clinical parameters. Additionally, immunohistochemical staining for YKL-40 was performed in lung specimens of IPF patients and control subjects.

RESULTS

Serum and BALF YKL-40 levels were significantly higher in IPF than in controls (serum: 245.8+/-180.2ng/ml vs. 116.0+/-58.3ng/ml; BALF: 17.8+/-19.1ng/ml vs. 0.3+/-0.9ng/ml, respectively). Serum YKL-40 levels significantly correlated positively with serum KL-6 levels and AaDO(2), and negatively with DLco and PaO(2). Immunohistochemical study revealed enhanced YKL-40 expression in alveolar macrophages and bronchiolar epithelia adjacent to fibrotic lesions in IPF, but not in controls.

CONCLUSIONS

These data suggest that YKL-40 is increased in the circulation and lungs of IPF patients, suggesting that this glycoprotein is associated with the pathophysiology of IPF.

摘要

背景

YKL-40 是一种哺乳动物几丁质酶样蛋白,已被证明在导致组织重塑和纤维化的病理条件中发挥作用。最近,在严重哮喘中发现 YKL-40 增加,表明 YKL-40 有助于气道重塑;然而,关于特发性肺纤维化 (IPF) 中 YKL-40 的表达尚无数据。本研究旨在探讨 YKL-40 在 IPF 患者血清和肺中的表达,并确定其临床意义。

方法

使用酶联免疫吸附试验测量 63 例 IPF 患者血清和 18 例 IPF 患者支气管肺泡灌洗液 (BALF)中的 YKL-40 水平。还评估了健康受试者血清和 BALF 中的 YKL-40 水平。我们进一步研究了血清 YKL-40 水平与临床参数之间的关系。此外,对 IPF 患者和对照肺组织进行 YKL-40 的免疫组织化学染色。

结果

IPF 患者血清和 BALF 中的 YKL-40 水平明显高于对照组(血清:245.8+/-180.2ng/ml 与 116.0+/-58.3ng/ml;BALF:17.8+/-19.1ng/ml 与 0.3+/-0.9ng/ml)。血清 YKL-40 水平与血清 KL-6 水平和 AaDO(2)呈正相关,与 DLco 和 PaO(2)呈负相关。免疫组织化学研究显示,在 IPF 纤维化病变附近的肺泡巨噬细胞和细支气管上皮中,YKL-40 的表达增强,但在对照组中没有。

结论

这些数据表明 YKL-40 在 IPF 患者的循环和肺部中增加,表明该糖蛋白与 IPF 的病理生理学有关。

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