title: TIMP-2-derived 18-mer peptide inhibits endothelial cell proliferation and migration through cAMP/PKA-dependent mechanism.
abstract: In the present study, we report the regulatory effects and molecular mechanisms of integrin α3β1-binding tissue inhibitor of metalloproteinases-2 (TIMP-2) 18-mer peptide (peptide 9) on proliferation, migration and tubular formation in human umbilical vein endothelial cells. Peptide 9 markedly inhibits vascular endothelial growth factor-A-stimulated cell proliferation. This anti-proliferative activity of peptide 9 is mediated by cAMP/protein kinase A (PKA)-dependent induction of p27(Kip1) expression as evidenced by using adenylate cyclase inhibitor SQ22536 or PKA inhibitor H89. Peptide 9-mediated inhibition of endothelial cell migration and tubular formation is also dependent on cAMP/PKA activity. Collectively, our findings clearly show the pharmacological roles and action mechanism of peptide 9 in regulating angiogenic responses through cAMP/PKA activity, and support further development as a potential therapeutics for the treatment of angiogenesis-related disorders including cancer.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Hyeon-Ju
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Young-Rak
authors.initials: YR
authors.lastname: Cho
authors.affiliation: Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Soo Hyeon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan 330-714, Republic of Korea. Electronic address: dwseomb@dankook.ac.kr.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Seo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D010455:Peptides / Q000235:genetics / Q000494:pharmacology*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D010455:Peptides; C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Angiogenesis; Integrin α3β1; Peptide 9; Protein kinase A; TIMP-2; cAMP