A Lipidomics Approach to Identifying Key Lipid Species Involved in VEGF-Inhibitor Mediated Attenuation of Bleomycin-Induced Pulmonary Fibrosis

被引：23

作者：

Kulkarni, Yogesh M. ^{[1
]}

Dutta, Sucharita ^{[2
]}

Iyer, Anand Krishnan V. ^{[1
]}

Wright, Clayton A. ^{[1
]}

Ramesh, Vani ^{[3
]}

Kaushik, Vivek ^{[1
]}

Semmes, Oliver John ^{[2
,4
]}

Azad, Neelam ^{[1
]}

机构：

[1] Hampton Univ, Sch Pharm, Dept Pharmaceut Sci, Hampton, VA 23668 USA

[2] Eastern Virginia Med Sch, Canc Res Ctr, Norfolk, VA 23501 USA

[3] Eastern Virginia Med Sch, Jones Inst Reprod Med, Dept Obstet & Gynecol, Norfolk, VA USA

[4] Eastern Virginia Med Sch, Dept Microbiol & Mol Cell Biol, Norfolk, VA 23501 USA

来源：

PROTEOMICS CLINICAL APPLICATIONS | 2018年 / 12卷 / 03期

基金：

美国国家卫生研究院;

关键词：

bleomycin; ingenuity pathway analysis; lipidomics; pulmonary fibrosis; VEGF-inhibitor; THERAPEUTIC TARGET; MEMBRANE-LIPIDS; PHOSPHOLIPASE-C; MESSENGER-RNA; GROWTH-FACTOR; LYSOPHOSPHATIDYLCHOLINE; PHOSPHATIDYLETHANOLAMINE; METABOLISM; LUNG; DIACYLGLYCEROL;

D O I：

10.1002/prca.201700086

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

PurposePoor molecular characterization of idiopathic pulmonary fibrosis (IPF) has led to insufficient understanding of the pathogenesis of the disease, resulting in lack of effective therapies and poor prognosis. Particularly, the role of lipid imbalance due to impaired lipid metabolism in the pathogenesis of IPF has been poorly studied. Experimental designThe authors have used shotgun lipidomics in a bleomycin (BLM) mouse model of pulmonary fibrosis with vascular endothelial growth factor (VEGF)-inhibitor CBO-P11 as a therapeutic measure, to identify a comprehensive set of lipids that contribute to the pathogenesis of pulmonary fibrosis. ResultsThe authors report that attenuation of BLM-induced fibrotic response with CBO-P11 cotreatment is accompanied by a decrease in total lipid content and specific downregulation of lipids, which are upregulated in response to BLM treatment. Conclusion and clinical relevanceDysregulated lipids identified in this study hold the potential of being future biomarkers for IPF.

引用

页数：9

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