Chai Tianci, Liu Yinji, Zeng Yuwei, Kang Sung-Yoon, Li Jie
Key Laboratory of Shenzhen Respiratory Disease, Shenzhen Institute of Respiratory Disease, Shenzhen People's Hospital (The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University), Shenzhen, China.
Division of Pulmonology and Allergy, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.
J Thorac Dis. 2024 Oct 31;16(10):6955-6968. doi: 10.21037/jtd-24-1366. Epub 2024 Oct 28.
Asthma is a chronic respiratory disease that affects billions of people. Due to its diverse phenotypes and endotypes with distinct pathophysiological mechanisms, significant challenges arise in its clinical diagnosis and treatment. The discovery of potential biomarkers of asthma has significant implications for its clinical classification and precise treatment. The purpose of this study is to identify potential biomarkers for asthma, providing a foundation for its diagnosis and treatment.
We constructed an ovalbumin (OVA)-sensitized asthmatic mice model and used isobaric Tags for Relative and Absolute Quantitation (iTRAQ) labeling and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) technology to identify differentially expressed proteins (DEPs) in lung tissues. We then performed enrichment analyses of the DEPs using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and constructed protein-protein interaction (PPI) networks.
We identified 242 DEPs in the asthmatic mice model and showed that heat shock protein family A (Hsp70) member 5 (HSPA5) is a central protein in asthma. Consistent with our bioinformatics analysis, our western blot validation confirmed that the protein levels of arginase 1 (ARG1), chitinase-like protein 3 (CHIL3), chloride channel accessory 1 (CLCA1), and bactericidal/permeability-increasing protein (BPI) fold-containing family B member 1 (BPIFB1) were significantly increased in asthma group compared to the control group. Thus, we found that CLCA1 and BPIFB1 were the most promising potential biomarkers of asthma.
Our iTRAQ analysis and western blot verification of asthmatic mice showed that HSPA5 is a central protein in asthma, and CLCA1 and BPIFB1 are novel potential biomarkers that could play significant roles in the diagnosis and treatment of asthma.
哮喘是一种影响数十亿人的慢性呼吸道疾病。由于其具有不同的表型和内型,且病理生理机制各异,其临床诊断和治疗面临重大挑战。哮喘潜在生物标志物的发现对其临床分类和精准治疗具有重要意义。本研究旨在识别哮喘的潜在生物标志物,为其诊断和治疗提供依据。
我们构建了卵清蛋白(OVA)致敏的哮喘小鼠模型,并使用相对和绝对定量同位素标记(iTRAQ)以及液相色谱-质谱联用(LC-MS/MS)技术来鉴定肺组织中差异表达的蛋白质(DEPs)。然后,我们使用基因本体论(GO)和京都基因与基因组百科全书(KEGG)数据库对这些DEPs进行富集分析,并构建蛋白质-蛋白质相互作用(PPI)网络。
我们在哮喘小鼠模型中鉴定出242个DEPs,并表明热休克蛋白家族A(Hsp70)成员5(HSPA5)是哮喘中的核心蛋白。与我们的生物信息学分析一致,我们的蛋白质印迹验证证实,与对照组相比,哮喘组中精氨酸酶1(ARG1)、几丁质酶样蛋白3(CHIL3)、氯离子通道辅助蛋白1(CLCA1)和含杀菌/通透性增加蛋白(BPI)折叠家族B成员1(BPIFB1)的蛋白水平显著升高。因此,我们发现CLCA1和BPIFB1是哮喘最有前景的潜在生物标志物。
我们对哮喘小鼠的iTRAQ分析和蛋白质印迹验证表明,HSPA5是哮喘中的核心蛋白,而CLCA1和BPIFB1是新型潜在生物标志物,可能在哮喘的诊断和治疗中发挥重要作用。