An Integrative Multiomics Framework for Identification of Therapeutic Targets in Pulmonary Fibrosis.
An Integrative Multiomics Framework for Identification of Therapeutic Targets in Pulmonary Fibrosis.
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用于识别肺纤维化治疗靶点的综合多组学框架。
DOI：
10.1002/advs.202207454
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发表时间：
2023-06
期刊：
影响因子：
15.1
通讯作者：
Cinar, Resat
中科院分区：
文献类型：
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作者：
Arif, Muhammad;Basu, Abhishek;Wolf, Kaelin M.;Park, Joshua K.;Pommerolle, Lenny;Behee, Madeline;Gochuico, Bernadette R.;Cinar, Resat
关键词：
肺纤维化（PF）是一种异质性疾病，预后差。因此，需要确定其他治疗方式来改善结局。然而，缺乏疾病进展的生物标志物阻碍了临床前到临床的转化过程。在这里，这项工作评估和确定肺功能，转录组学和代谢组学在小鼠肺在7，14，21和28天后，单剂量的口咽博来霉素进行性改变。通过整合多组学数据，这项工作确定了与转录组学和代谢组学以及肺功能中的多种关键病理变化相关的两个中心基因子网络。这项工作提出了一个基于多组学的框架，以建立博莱霉素诱导的小鼠PF模型和人类特发性肺纤维化之间的翻译联系，以确定可药物化的靶点并测试治疗候选物。这项工作还表明外周大麻素受体1（CB1R）拮抗作用是PF临床转化的合理治疗靶点。小鼠肺纤维化图谱可以在https://niaaa.nih.gov/mouselungfibrosisatlas上免费访问。多组学方法有助于在人类及其小鼠实验模型之间建立特发性肺纤维化（IPF）的翻译联系。基于多组学的框架有助于识别IPF中的可用药靶点。系统药理学支持大麻素CB1R拮抗作用作为IPF的合理治疗策略。
Pulmonary fibrosis (PF) is a heterogeneous disease with a poor prognosis. Therefore, identifying additional therapeutic modalities is required to improve outcome. However, the lack of biomarkers of disease progression hampers the preclinical to clinical translational process. Here, this work assesses and identifies progressive alterations in pulmonary function, transcriptomics, and metabolomics in the mouse lung at 7, 14, 21, and 28 days after a single dose of oropharyngeal bleomycin. By integrating multi‐omics data, this work identifies two central gene subnetworks associated with multiple critical pathological changes in transcriptomics and metabolomics as well as pulmonary function. This work presents a multi‐omics‐based framework to establish a translational link between the bleomycin‐induced PF model in mice and human idiopathic pulmonary fibrosis to identify druggable targets and test therapeutic candidates. This work also indicates peripheral cannabinoid receptor 1 (CB1R) antagonism as a rational therapeutic target for clinical translation in PF. Mouse Lung Fibrosis Atlas can be accessed freely at https://niaaa.nih.gov/mouselungfibrosisatlas. Multi‐omics approach helps to establish a translational link in idiopathic pulmonary fibrosis (IPF) between human and its experimental model in mice. Multi‐omics‐based framework assists the identification of druggable targets in IPF. Systems pharmacology endorses cannabinoid CB1R antagonism as a rational therapeutic strategy in IPF.
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影响因子：
14.9
作者：
Howe KL;Achuthan P;Allen J;Allen J;Alvarez-Jarreta J;Amode MR;Armean IM;Azov AG;Bennett R;Bhai J;Billis K;Boddu S;Charkhchi M;Cummins C;Da Rin Fioretto L;Davidson C;Dodiya K;El Houdaigui B;Fatima R;Gall A;Garcia Giron C;Grego T;Guijarro-Clarke C;Haggerty L;Hemrom A;Hourlier T;Izuogu OG;Juettemann T;Kaikala V;Kay M;Lavidas I;Le T;Lemos D;Gonzalez Martinez J;Marugán JC;Maurel T;McMahon AC;Mohanan S;Moore B;Muffato M;Oheh DN;Paraschas D;Parker A;Parton A;Prosovetskaia I;Sakthivel MP;Salam AIA;Schmitt BM;Schuilenburg H;Sheppard D;Steed E;Szpak M;Szuba M;Taylor K;Thormann A;Threadgold G;Walts B;Winterbottom A;Chakiachvili M;Chaubal A;De Silva N;Flint B;Frankish A;Hunt SE;IIsley GR;Langridge N;Loveland JE;Martin FJ;Mudge JM;Morales J;Perry E;Ruffier M;Tate J;Thybert D;Trevanion SJ;Cunningham F;Yates AD;Zerbino DR;Flicek P
通讯作者：
Flicek P
iDREM：动态监管网络的交互式可视化。
影响因子：
4.3
作者：
Ding J;Hagood JS;Ambalavanan N;Kaminski N;Bar-Joseph Z
通讯作者：
Bar-Joseph Z
影响因子：
8
作者：
Alzaid, Fawaz;Lagadec, Floriane;Venteclef, Nicolas
通讯作者：
Venteclef, Nicolas
影响因子：
3.1
作者：
Estany S;Vicens-Zygmunt V;Llatjós R;Montes A;Penín R;Escobar I;Xaubet A;Santos S;Manresa F;Dorca J;Molina-Molina M
通讯作者：
Molina-Molina M
影响因子：
82.9
作者：
通讯作者：
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