Sokai Akihiko, Handa Tomohiro, Tanizawa Kiminobu, Oga Toru, Uno Kazuko, Tsuruyama Tatsuaki, Kubo Takeshi, Ikezoe Kohei, Nakatsuka Yoshinari, Tanimura Kazuya, Muro Shigeo, Hirai Toyohiro, Nagai Sonoko, Chin Kazuo, Mishima Michiaki
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.
Department of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.
Respir Res. 2015 Sep 29;16:120. doi: 10.1186/s12931-015-0280-9.
Matrix metalloproteinases (MMPs) are believed to be involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF), and MMP-7 has been described as a useful biomarker for IPF. However, little is known regarding the significance of MMP-10 as a biomarker for IPF.
This observational cohort study included 57 patients with IPF. Serum MMPs were comprehensively measured in all patients, and the relationships between these markers and both disease severity and prognosis were evaluated. Bronchoalveolar lavage fluid (BALF) MMP-7 and -10 levels were measured in 19 patients to investigate the correlation between these markers and their corresponding serum values. Immunohistochemical staining for MMP-10 was also performed in IPF lung tissue.
Serum MMP-7 and -10 levels correlated significantly with both the percentage of predicted forced vital capacity (ρ = -0.31, p = 0.02 and ρ = -0.34, p < 0.01, respectively) and the percentage of predicted diffusing capacity of the lung for carbon monoxide (ρ = -0.32, p = 0.02 and ρ = -0.43, p < 0.01, respectively). BALF MMP-7 and -10 levels correlated with their corresponding serum concentrations. Only serum MMP-10 predicted clinical deterioration within 6 months and overall survival. In IPF lungs, the expression of MMP-10 was enhanced and localized to the alveolar epithelial cells, macrophages, and peripheral bronchiolar epithelial cells.
MMP-10 may be a novel biomarker reflecting both disease severity and prognosis in patients with IPF.
基质金属蛋白酶（MMPs）被认为参与特发性肺纤维化（IPF）的发病机制，且MMP - 7已被描述为IPF的一种有用生物标志物。然而，关于MMP - 10作为IPF生物标志物的意义知之甚少。
这项观察性队列研究纳入了57例IPF患者。对所有患者全面检测血清MMPs，并评估这些标志物与疾病严重程度和预后的关系。对19例患者检测支气管肺泡灌洗液（BALF）中的MMP - 7和 - 10水平，以研究这些标志物与其相应血清值之间的相关性。还对IPF肺组织进行了MMP - 10的免疫组织化学染色。
血清MMP - 7和 - 10水平与预测用力肺活量百分比（分别为ρ = -0.31，p = 0.02和ρ = -0.34，p < 0.01）以及预测肺一氧化碳弥散量百分比（分别为ρ = -0.32，p = 0.02和ρ = -0.43，p < 0.01）均显著相关。BALF中MMP - 7和 - 10水平与其相应血清浓度相关。仅血清MMP - 10可预测6个月内的临床恶化和总生存期。在IPF肺组织中，MMP - 10的表达增强，并定位于肺泡上皮细胞、巨噬细胞和外周细支气管上皮细胞。
MMP - 10可能是反映IPF患者疾病严重程度和预后的一种新型生物标志物。
