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循环分泌球蛋白家族1A成员1(SCGB1A1)水平作为生物质烟雾诱导的慢性阻塞性肺疾病的标志物

Circulating Secretoglobin Family 1A Member 1 (SCGB1A1) Levels as a Marker of Biomass Smoke Induced Chronic Obstructive Pulmonary Disease.

作者信息

Veerapaneni Vivek Vardhan, Upadhyay Swapna, Thimraj Tania A, Siddaiah Jayaraj Biligere, Krishnarao Chaya Sindaghatta, Lokesh Komarla Sundararaja, Thimmulappa Rajesh, Palmberg Lena, Ganguly Koustav, Anand Mahesh Padukudru

机构信息

Department of Pulmonary Medicine, JSS Medical College and Hospital, JSS Academy of Higher Education and Research, Mysuru 570015, India.

Unit of Integrative Toxicology, Institute of Environmental Medicine (IMM), Karolinska Institutet, 17177 Stockholm, Sweden.

出版信息

Toxics. 2021 Aug 31;9(9):208. doi: 10.3390/toxics9090208.

Abstract

Secretoglobin family 1A member 1 (SCGB1A1) alternatively known as club cell protein 16 is a protective pneumo-protein. Decreased serum levels of SCGB1A1 have been associated with tobacco smoke induced chronic obstructive pulmonary disease (TS-COPD). Exposure to biomass smoke (BMS) is an important COPD risk factor among women in low and lower-middle income countries. Therefore, in a cross-sectional study ( = 50/group; total 200 subjects) we assessed serum SCGB1A1 levels in BMS-COPD subjects (11 male, 39 female) compared to TS-COPD (all male) along with TS-CONTROL (asymptomatic smokers, all male) and healthy controls (29 male, 21 female) in an Indian population. Normal and chronic bronchitis like bronchial mucosa models developed at the air-liquid interface using human primary bronchial epithelial cells (3 donors, and three replicates per donor) were exposed to cigarette smoke condensate (CSC; 0.25, 0.5, and 1%) to assess SCGB1A1 transcript expression and protein secretion. Significantly ( < 0.0001) decreased serum SCGB1A1 concentrations (median, interquartile range, ng/mL) were detected in both BMS-COPD (1.6; 1.3-2.4) and TS-COPD (1.8; 1.4-2.5) subjects compared to TS-CONTROL (3.3; 2.9-3.5) and healthy controls (5.1; 4.5-7.2). The levels of SCGB1A1 were positively correlated ( = 0.7-0.8; < 0.0001) with forced expiratory volume in 1 s, forced vital capacity, their ratios, and exercise capacity. The findings are also consistent within the BMS-COPD sub-group as well. Significantly ( < 0.03) decreased SCGB1A1 concentrations were detected with severity of COPD, dyspnea, quality of life, and mortality indicators. In vitro studies demonstrated significantly ( < 0.05) decreased SCGB1A1 transcript and/or protein levels following CSC exposure. Circulating SCGB1A1 levels may therefore also be considered as a potent marker of BMS-COPD and warrant studies in larger independent cohorts.

摘要

分泌球蛋白家族1A成员1(SCGB1A1),也被称为克拉拉细胞蛋白16,是一种具有保护作用的肺蛋白。血清中SCGB1A1水平降低与烟草烟雾诱导的慢性阻塞性肺疾病(TS - COPD)有关。在低收入和中低收入国家的女性中,接触生物质烟雾(BMS)是慢性阻塞性肺疾病的一个重要危险因素。因此,在一项横断面研究中(每组50人;共200名受试者),我们评估了印度人群中BMS - COPD受试者(11名男性,39名女性)与TS - COPD受试者(均为男性)、TS - 对照(无症状吸烟者,均为男性)和健康对照(29名男性,21名女性)的血清SCGB1A1水平。使用人原代支气管上皮细胞(3名供体,每个供体三个重复)在气液界面建立的正常和类似慢性支气管炎的支气管黏膜模型,暴露于香烟烟雾冷凝物(CSC;0.25%、0.5%和1%)中,以评估SCGB1A1转录本表达和蛋白分泌。与TS - 对照(3.3;2.9 - 3.5)和健康对照(5.1;4.5 - 7.2)相比,在BMS - COPD(1.6;1.3 - 2.4)和TS - COPD(1.8;1.4 - 2.5)受试者中均检测到血清SCGB1A1浓度显著降低(<0.0001)。SCGB1A1水平与第1秒用力呼气量、用力肺活量、它们的比值以及运动能力呈正相关(=0.7 - 0.8;<0.0001)。这些发现也在BMS - COPD亚组中保持一致。随着慢性阻塞性肺疾病的严重程度、呼吸困难、生活质量和死亡率指标的增加,SCGB1A1浓度显著降低(<0.03)。体外研究表明,CSC暴露后SCGB1A1转录本和/或蛋白水平显著降低(<0.05)。因此,循环中的SCGB1A1水平也可被视为BMS - COPD的一个有效标志物,值得在更大的独立队列中进行研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0150/8472904/229324fc8b72/toxics-09-00208-g001.jpg

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