title: Fibronectin and vitronectin induce AP-1-mediated matrix metalloproteinase-9 expression through integrin α(5)β(1)/α(v)β(3)-dependent Akt, ERK and JNK signaling pathways in human umbilical vein endothelial cells.
abstract: The activity of matrix metalloproteinases (MMPs), which selectively degrades the extracellular matrix (ECM), is critical in angiogenesis. Conversely, changes in ECM composition/structure alter the expression and activity of MMPs in various cell types. In the present study, we examined whether changes in ECM composition affect MMPs expression/activity of endothelial cells and thereby alter the surrounding ECM structure. Among the ECM molecules examined, fibronectin (FN) and vitronectin (VN) increased the expression and activity of MMP-9 in human umbilical vein endothelial cells (HUVECs). Both α(5)β(1) and α(v)β(3) integrins were involved in FN-induced MMP-9 expression. Also, FN-induced MMP-9 expression was found to be mediated by AP-1 transcription factors, including c-Jun, JunB, and JunD. Inhibitors or siRNAs specific to AP-1 activating signal transducers, including FAK-Src, PI3K/Akt, ERK, and JNK, abolished both FN-induced AP-1 activation and MMP-9 expression. VN-induced AP-1 activation and MMP-9 expression were also mediated by these AP-1 activating signal transducers in addition to p38 MAPK. Moreover, treatment with FN or VN resulted in increased degradation of collagen on HUVEC culture plates. Taken together, our data suggest that both fibronectin and vitronectin induce MMP-9 expression via the AP-1-activating signaling pathways in endothelial cells, and thereby stimulate degradation of surrounding collagen, leading to alterations in ECM structure and potentially the promotion of angiogenesis.
authors.affiliation: Medical and Bio-Material Research Center, Kangwon National University, Kangwon-do, Republic of Korea.
authors.forename: Young-June
authors.initials: YJ
authors.lastname: Jin
authors.forename: Iha
authors.initials: I
authors.lastname: Park
authors.forename: In-Kee
authors.initials: IK
authors.lastname: Hong
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Byun
authors.forename: Jeongsuk
authors.initials: J
authors.lastname: Choi
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.forename: Hansoo
authors.initials: H
authors.lastname: Lee
mesh_terms: D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005353:Fibronectins / Q000494:pharmacology*; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology; D019096:Vitronectin / Q000494:pharmacology*
chemical_list: D005353:Fibronectins; D039081:Integrin alpha5beta1; D039302:Integrin alphaVbeta3; D016023:Integrins; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1; D019096:Vitronectin; D003094:Collagen; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9