TY - JOUR
T1 - Angiogenesis-associated crosstalk between collagens, CXC chemokines, and thrombospondin domain-containing proteins
AU - Rivera, Corban G.
AU - Bader, Joel S.
AU - Popel, Aleksander S.
PY - 2011/8/1
Y1 - 2011/8/1
N2 - Excessive vascularization is a hallmark of many diseases including cancer, rheumatoid arthritis, diabetic nephropathy, pathologic obesity, age-related macular degeneration, and asthma. Compounds that inhibit angiogenesis represent potential therapeutics for many diseases. Karagiannis and Popel [Proc. Natl. Acad. Sci. USA 105(37):13775-13780, 2008] used a bioinformatics approach to identify more than 100 peptides with sequence homology to known angiogenesis inhibitors. The peptides could be grouped into families by the conserved domain of the proteins they were derived from. The families included type IV collagen fibrils, CXC chemokine ligands, and type I thrombospondin domain-containing proteins. The relationships between these families have received relatively little attention. To investigate these relationships, we approached the problem by placing the families of proteins in the context of the human interactome including >120,000 physical interactions among proteins, genes, and transcripts. We built on a graph theoretic approach to identify proteins that may represent conduits of crosstalk between protein families. We validated these findings by statistical analysis and analysis of a time series gene expression data set taken during angiogenesis. We identified six proteins at the center of the angiogenesis-associated network including three syndecans, MMP9, CD44, and versican. These findings shed light on the complex signaling networks that govern angiogenesis phenomena.
AB - Excessive vascularization is a hallmark of many diseases including cancer, rheumatoid arthritis, diabetic nephropathy, pathologic obesity, age-related macular degeneration, and asthma. Compounds that inhibit angiogenesis represent potential therapeutics for many diseases. Karagiannis and Popel [Proc. Natl. Acad. Sci. USA 105(37):13775-13780, 2008] used a bioinformatics approach to identify more than 100 peptides with sequence homology to known angiogenesis inhibitors. The peptides could be grouped into families by the conserved domain of the proteins they were derived from. The families included type IV collagen fibrils, CXC chemokine ligands, and type I thrombospondin domain-containing proteins. The relationships between these families have received relatively little attention. To investigate these relationships, we approached the problem by placing the families of proteins in the context of the human interactome including >120,000 physical interactions among proteins, genes, and transcripts. We built on a graph theoretic approach to identify proteins that may represent conduits of crosstalk between protein families. We validated these findings by statistical analysis and analysis of a time series gene expression data set taken during angiogenesis. We identified six proteins at the center of the angiogenesis-associated network including three syndecans, MMP9, CD44, and versican. These findings shed light on the complex signaling networks that govern angiogenesis phenomena.
KW - Angiogenesis
KW - CXC chemokine
KW - Crosstalk
KW - Interactome
KW - Syndecan
KW - Thrombospondin-1
KW - Type IV collagen
UR - http://www.scopus.com/inward/record.url?scp=80051547835&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80051547835&partnerID=8YFLogxK
U2 - 10.1007/s10439-011-0325-2
DO - 10.1007/s10439-011-0325-2
M3 - Article
C2 - 21590489
AN - SCOPUS:80051547835
VL - 39
SP - 2213
EP - 2222
JO - Annals of Biomedical Engineering
JF - Annals of Biomedical Engineering
SN - 0090-6964
IS - 8
ER -