Proteome profiling in IL-1β and VEGF-activated human umbilical vein endothelial cells delineates the interlink between inflammation and angiogenesis

被引:72
作者
Mohr, Thomas [1 ,2 ]
Haudek-Prinz, Verena [3 ]
Slany, Astrid [1 ,3 ]
Grillari, Johannes [4 ,5 ]
Micksche, Michael [1 ]
Gerner, Christopher [3 ]
机构
[1] Med Univ Vienna, Dept Med, Inst Canc Res, Vienna, Austria
[2] ScienceConsult DI Thomas Mohr KG, Guntramsdorf, Austria
[3] Univ Vienna, Dept Analyt Chem, Fac Chem, Vienna, Austria
[4] BOKU Univ Life Sci, Dept Biotechnol, Christian Doppler Lab Biotechnol Skin Aging, Vienna, Austria
[5] Evercyte GmbH, Vienna, Austria
关键词
GENE ONTOLOGY; SECRETOME; MECHANISMS; EXPRESSION; INSIGHTS; DISEASE; BINDING;
D O I
10.1371/journal.pone.0179065
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Endothelial cells represent major effectors in inflammation and angiogenesis, processes that drive a multitude of pathological states such as atherosclerosis and cancer. Both inflammation and angiogenesis are interconnected with each other in the sense that many proinflammatory proteins possess proangiogenic properties and vice versa. To elucidate this interplay further, we present a comparative proteome study of inflammatory and angiogenic activated endothelial cells. HUVEC were stimulated with interleukin 1-beta and VEGF, respectively. Cultured primary cells were fractionated into secreted, cytoplasmic and nuclear protein fractions and processed for subsequent LC-MS/MS analysis. Obtained protein profiles were filtered for fraction-specific proteins to address potential cross fractional contamination, subjected to comparative computational biology analysis ( GO-Term enrichment analysis, weighted gene co-expression analysis) and compared to published mRNA profiles of IL-1 beta respectively VEGF stimulated HUVEC. GO Term enrichment analysis and comparative pathway analysis revealed features such as NOD and NfkB signaling for inflammatory activated HUVEC and VEGF and ErB signaling for VEGF-activated HUVEC with potential crosstalk via map kinases MAP2K2. Weighted protein co-expression network analysis revealed several potential hub genes so far not associated with driver function in inflammation or angiogenesis such as HSPG2, ANXA3, and GPI. "Classical" inflammation or angiogenesis markers such as IL6, CXCL8 or CST1 were found in a less central position within the co-expression networks. In conclusion, this study reports a framework for the computational biology based analysis of proteomics data applied to cytoplasmic, nucleic and extracellular fractions of quiescent, inflammatory and angiogenic activated HUVEC. Novel potential hub genes relevant for these processes were successfully identified.
引用
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页数:23
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