Activation of the ERK signaling pathway is involved in CD151-induced angiogenic effects on the formation of CD151-integrin complexes.
OBJECTIVE
To assess the roles of extracellular signal-regulated kinase (ERK), p38, and CD151-integrin complexes on proliferation, migration, and tube formation activities of CD151-induced human umbilical vein endothelial cells (HUVECs).


METHODS
CD151, anti-CD151 and CD151-AAA mutant were inserted into recombinant adeno-associated virus (rAAV) vectors and used to transfect HUVECs. After transfection, the expression of CD151 was measured. Proliferation was assessed using the 3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. Cell migration was evaluated in Boyden transwell chambers using FBS as the chemotactic stimulus. The tube formation assay was performed on matrigel. The potential involvement of various signaling pathways was explored using selective inhibitors.


RESULTS
CD151 gene delivery increased the expression of CD151 at both the mRNA and protein levels. Overexpression of CD151 promoted cell proliferation, migration and tube formation in vitro, and phosphorylation of ERK was also increased. Further, CD151-induced cell proliferation, migration, and tube formation were attenuated by the ERK inhibitor PD98059 (20 micromol/L) but not by a p38 inhibitor (SB203580, 20 micromol/L). Moreover, there was no significant difference in CD151 protein expression between the CD151 group and the CD151-AAA group, but the CD151-AAA mutant abrogated cellular proliferation, migration, and tube formation and decreased the phosphorylation of ERK.


CONCLUSIONS
This study suggests that activation of the ERK signaling pathway may be involved in the angiogenic effects of CD151. Activation of ERK was dependent on the formation of CD151-integrin complexes. Therefore modulation of CD151 may be as a novel therapeutic strategy for regulating angiogenesis.
Zuo
Hou-juan
HJ
Department of Cardiology of Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Lin
Jing-yang
JY
Liu
Zhao-yu
ZY
Liu
Wei-feng
WF
Liu
Tao
T
Yang
Jun
J
Liu
Yu
Y
Wang
Dao-wen
DW
Liu
Zheng-xiang
ZX
D015703:Antigens, CD / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D018014:Gene Transfer Techniques; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D010766:Phosphorylation; D015398:Signal Transduction; D060185:Tetraspanin 24; D014162:Transfection; D014471:Umbilical Veins; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D015703:Antigens, CD; C554715:CD151 protein, human; D016023:Integrins; D060185:Tetraspanin 24; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases