Identification of Genetic Signature Associated With Aging in Pulmonary Fibrosis.
Identification of Genetic Signature Associated With Aging in Pulmonary Fibrosis.
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DOI：
10.3389/fmed.2021.744239
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发表时间：
2021
影响因子：
3.9
通讯作者：
Xie J
中科院分区：
文献类型：
--
作者：
Lu Y;Chen J;Wang S;Tian Z;Fan Y;Wang M;Zhao J;Tang K;Xie J
背景：衰老是特发性肺纤维化（IPF）的一个重要危险因素和独立预后因素。在本研究中，我们旨在基于基因表达谱对衰老在肺纤维化中的作用进行全面分析。方法：从基因表达综合库 (GEO) 获得临床 IPF 患者的 4 个数据集（GSE21411、GSE24206、GSE47460 和 GSE101286）和博来霉素 (BLM) 诱导的肺纤维化 (BIPF) 小鼠模型 (GSE123293) 的数据集。根据不同年龄范围，将IPF和BIPF小鼠分为年轻组和老年组。使用基因本体论（GO）功能、京都基因和基因组百科全书（KEGG）和中心基因分析对差异表达基因（DEG）进行系统分析。最后，我们在体内验证了年龄和与年龄相关的核心基因的作用。结果：通过比较老年和年轻 IPF 患者的表达谱，我们鉴定了 108 个与衰老相关的 DEG，其中 21 个上调，87 个下调。 DEG 与 GO 生物过程 (BP) 中的“对糖皮质激素的反应”、“对皮质类固醇的反应”和“节律过程”相关。对于KEGG分析，DEG中显着富集的前三个KEGG通路包括“IL-17信号通路”、“矿物质吸收”和“HIF-1信号通路”。通过老年和年轻BIPF小鼠的比较，共鉴定出778个与衰老相关的DEG，其中453个基因增加，325个基因减少。对于 GO 和 KEGG 分析，DEG 富含细胞外基质 (ECM) 和胶原代谢。 IPF患者和BIPF小鼠的常见DEG在BP类别中丰富，包括“细菌凝集的诱导”、“透明质酸生物合成过程”和“异型细胞间粘附的正向调节”。我们证实老年 BIPF 小鼠出现更严重的肺纤维化。最后，四个与衰老相关的核心基因（Slc2a3、Fga、Hp和Thbs1）在体内得到验证。结论：这项研究为衰老对肺纤维化的影响提供了新的见解。我们还确定了与肺纤维化发展相关的四个与衰老相关的核心基因（Slc2a3、Fga、Hp 和 Thbs1）。
Background: Aging is a strong risk factor and an independent prognostic factor in idiopathic pulmonary fibrosis (IPF). In this study, we aimed to conduct a comprehensive analysis based on gene expression profiles for the role of aging in pulmonary fibrosis. Method: Four datasets (GSE21411, GSE24206, GSE47460, and GSE101286) for patients with clinical IPF and one dataset for bleomycin (BLM)-induced pulmonary fibrosis (BIPF) mouse model (GSE123293) were obtained from Gene Expression Omnibus (GEO). According to different age ranges, both patients with IPF and BIPF mice were divided into young and aged groups. The differently expressed genes (DEGs) were systemically analyzed using Gene Ontology (GO) functional, Kyoto Encyclopedia of Genes and Genomes (KEGG), and hub genes analysis. Finally, we verified the role of age and core genes associated with age in vivo. Results: Via the expression profile comparisons of aged and young patients with IPF, we identified 108 aging-associated DEGs, with 21 upregulated and 87 downregulated. The DEGs were associated with “response to glucocorticoid,” “response to corticosteroid,” and “rhythmic process” in GO biological process (BP). For KEGG analysis, the top three significantly enriched KEGG pathways of the DEGs included “IL-17 signaling pathway,” “Mineral absorption,” and “HIF-1-signaling pathway.” Through the comparisons of aged and young BIPF mice, a total number of 778 aging-associated DEGs were identified, with 453 genes increased and 325 genes decreased. For GO and KEGG analysis, the DEGs were enriched in extracellular matrix (ECM) and collagen metabolism. The common DEGs of patients with IPF and BIPF mice were enriched in the BP category, including “induction of bacterial agglutination,” “hyaluronan biosynthetic process,” and “positive regulation of heterotypic cell-cell adhesion.” We confirmed that aged BIPF mice developed more serious pulmonary fibrosis. Finally, the four aging-associated core genes (Slc2a3, Fga, Hp, and Thbs1) were verified in vivo. Conclusion: This study provides new insights into the impact of aging on pulmonary fibrosis. We also identified four aging-associated core genes (Slc2a3, Fga, Hp, and Thbs1) related to the development of pulmonary fibrosis.
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影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
影响因子：
82.9
作者：
Liang J;Zhang Y;Xie T;Liu N;Chen H;Geng Y;Kurkciyan A;Mena JM;Stripp BR;Jiang D;Noble PW
通讯作者：
Noble PW
影响因子：
4.3
作者：
Peikert, T.;Daniels, C. E.;Ryu, J. H.
通讯作者：
Ryu, J. H.
影响因子：
7.3
作者：
Sang X;Wang Y;Xue Z;Qi D;Fan G;Tian F;Zhu Y;Yang J
通讯作者：
Yang J
影响因子：
2.7
作者：
Cho JH;Gelinas R;Wang K;Etheridge A;Piper MG;Batte K;Dakhallah D;Price J;Bornman D;Zhang S;Marsh C;Galas D
通讯作者：
Galas D