Novel pathway compendium analysis elucidates mechanism of pro-angiogenic synthetic small molecule.

Bioinformatics
Kristen A WieghausJason A Papin

Abstract

Computational techniques have been applied to experimental datasets to identify drug mode-of-action. A shortcoming of existing approaches is the requirement of large reference databases of compound expression profiles. Here, we developed a new pathway-based compendium analysis that couples multi-timepoint, controlled microarray data for a single compound with systems-based network analysis to elucidate drug mechanism more efficiently. We applied this approach to a transcriptional regulatory footprint of phthalimide neovascular factor 1 (PNF1)-a novel synthetic small molecule that exhibits significant in vitro endothelial potency-spanning 1-48 h post-supplementation in human micro-vascular endothelial cells (HMVEC) to comprehensively interrogate PNF1 effects. We concluded that PNF1 first induces tumor necrosis factor-alpha (TNF-alpha) signaling pathway function which in turn affects transforming growth factor-beta (TGF-beta) signaling. These results are consistent with our previous observations of PNF1-directed TGF-beta signaling at 24 h, including differential regulation of TGF-beta-induced matrix metalloproteinase 14 (MMP14/MT1-MMP) which is implicated in angiogenesis. Ultimately, we illustrate how our pathway-based compendium...Continue Reading

References

Dec 15, 1988·Biochemical and Biophysical Research Communications·D M WisemanS J Leibovich
Aug 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·S M WahlM B Sporn
Jan 1, 2000·Cardiovascular Research·W Schaper, I Buschmann
Jan 3, 2001·Proceedings of the National Academy of Sciences of the United States of America·C Li, W H Wong
Feb 13, 2001·Cardiovascular Research·E M ConwayP Carmeliet
Nov 1, 2001·Annual Review of Cell and Developmental Biology·M D Sternlicht, Z Werb
Nov 29, 2001·Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology·N Van RoyenI Buschmann
Oct 5, 2002·Journal of Computer-aided Molecular Design·R D TaylorJ W Essex
May 22, 2003·The American Journal of Pathology·Sunfa Cheng, David H Lovett
Sep 25, 2003·Proceedings of the National Academy of Sciences of the United States of America·Brian P KelleyTrey Ideker
Jan 6, 2004·Nature Biotechnology·Joel S BaderJohn Chant
Jun 18, 2004·Nucleic Acids Research·Brandon Ason, William S Reznikoff
Jun 25, 2004·Nucleic Acids Research·Brian P KelleyTrey Ideker
Jan 18, 2005·American Journal of Respiratory Cell and Molecular Biology·Deborah E SullivanArnold R Brody
Feb 3, 2005·Proceedings of the National Academy of Sciences of the United States of America·Roded SharanTrey Ideker
Feb 11, 2005·Current Opinion in Chemical Biology·Rebecca A Butcher, Stuart L Schreiber
Mar 22, 2005·Experimental Physiology·Paolo Madeddu
May 5, 2005·Tissue Engineering·Eric M BreyLarry V McIntire
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Aug 8, 2006·Tissue Engineering·Kristen A WieghausEdward A Botchwey
Aug 29, 2007·Tissue Engineering·Kristen A WieghausEdward A Botchwey
Feb 7, 2008·Cardiovascular Research·Jean-Sebastien SilvestreBernard I Lévy
Sep 23, 2008·Biomaterials·Kristen A WieghausEdward A Botchwey

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Citations

Feb 4, 2010·Tissue Engineering. Part B, Reviews·Lauren S SefcikEdward A Botchwey
Apr 11, 2009·QJM : Monthly Journal of the Association of Physicians·Jeff Aronson
Sep 23, 2008·Biomaterials·Kristen A WieghausEdward A Botchwey
Mar 28, 2009·Biotechnology and Bioengineering·Kristen A WieghausEdward A Botchwey
Apr 2, 2009·Organogenesis·Lauren S SefcikEdward A Botchwey
Jun 5, 2015·Archives of Pharmacal Research·Hye Jin Jung, Ho Jeong Kwon
Apr 23, 2019·Regenerative Engineering and Translational Medicine·Anusuya DasEdward A Botchwey

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