McGee Sean P, Zhang Hongmei, Karmaus Wilfried, Sabo-Attwood Tara
Department of Environmental Health Sciences, University of South Carolina 921 Assembly Street, Columbia, SC, 29208, USA.
Division of Epidemiology, Biostatistics and Environmental Health, University of Memphis 3825 DeSoto Avenue, Memphis, TN 38152, USA.
Int J Mol Epidemiol Genet. 2014 May 29;5(2):71-86. eCollection 2014.
Epidemiological studies suggest sex-specific trends in the prevalence and mortality of idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) that are distinct for each disease. While the expression of numerous immune and extracellular matrix (ECM) genes in the lung have been well characterized in these diseases, associations elucidating their sex-specific expression patterns by disease type and severity, and the evaluation of hormone-related genes, have not been well studied. Here we performed targeted transcriptional profiling of 48 genes was performed on lung tissue samples from males and females with mild or medium severity IPF or COPD. The genes assessed included those involved in inflammation, ECM remodeling and hormonal processes. Data for 36 lung tissue samples were obtained that were stratified by disease and sex. Expression levels revealed a subset of genes which show differential expression among sexes, disease type, and disease severity. The most significant observations were the increased expression primarily of ECM genes in medium severity IPF (CATHK, COL1A1, COL3, MMP1, MMP7, IL-1RN) compared to mild IPF and COPD. Two genes, CH3L1 and MMP7 showed a tendency of interaction between sex and disease in IPF severity. Surprisingly, there were no significant differences in any of the sex genes measured between the IPF groups; however, ESR1 and AR expression levels were higher and lower, respectively, compared to COPD samples. Overall, this work highlights two genes, CH3L1 and MMP7, that may contribute to gender trends observed for IPF and COPD and are potential targets for future research.
流行病学研究表明，特发性肺纤维化（IPF）和慢性阻塞性肺疾病（COPD）在患病率和死亡率方面存在性别特异性趋势，且每种疾病的趋势各不相同。虽然在这些疾病中，肺内众多免疫和细胞外基质（ECM）基因的表达已得到充分表征，但按疾病类型和严重程度阐明其性别特异性表达模式以及评估激素相关基因之间的关联，尚未得到充分研究。在此，我们对患有轻度或中度严重程度IPF或COPD的男性和女性的肺组织样本进行了48个基因的靶向转录谱分析。评估的基因包括参与炎症、ECM重塑和激素过程的基因。获得了36个肺组织样本的数据，并按疾病和性别进行了分层。表达水平揭示了一部分基因在性别、疾病类型和疾病严重程度之间存在差异表达。最显著的观察结果是，与轻度IPF和COPD相比，中度严重程度IPF（组织蛋白酶K、I型胶原蛋白α1链、III型胶原蛋白、基质金属蛋白酶1、基质金属蛋白酶7、白细胞介素-1受体拮抗剂）中主要是ECM基因的表达增加。CH3L1和基质金属蛋白酶7这两个基因在IPF严重程度方面显示出性别与疾病之间的相互作用趋势。令人惊讶的是，在IPF组之间测量的任何性别基因均无显著差异；然而，与COPD样本相比，雌激素受体1（ESR1）和雄激素受体（AR）的表达水平分别更高和更低。总体而言，这项工作突出了CH3L1和基质金属蛋白酶7这两个基因，它们可能导致IPF和COPD中观察到的性别趋势，并且是未来研究的潜在靶点。
