AAMP Regulates Endothelial Cell Migration and Angiogenesis Through RhoA/Rho Kinase Signaling.
Angiogenesis is a complicated process including endothelial cell proliferation, migration and tube formation. AAMP plays a role in regulating cell migration of multiple cell types. The purpose of this study was to investigate whether AAMP regulates angiogenesis, and to clarify the role of AAMP in the VEGF-induced angiogenesis. We found that AAMP expressed in multiple cell types and mainly localized in cytoplasm and membrane in vascular endothelial cells. Using tube formation assay in vitro and aortic ring assay, siRNA-mediated knockdown and antibody blockade of AAMP impaired VEGF-induced endothelial cell tube formation and aortic ring angiogenic sprouting. Mechanistic studies showed that AAMP expression was significantly upregulated by VEGF in a concentration and time-dependent manner. Moreover, VEGF recruited AAMP to the cell membrane protrusions. AAMP regulates angiogenesis by mediating the spreading and migration of vascular endothelial cells. AAMP knock-down reduced VEGF-induced actin stress fibers and collagen gel contraction. Furthermore, we identified RhoA/Rho kinase signaling as an important factor that contributes to the action of AAMP in regulating endothelial cell migration and angiogenesis. Altogether, these data demonstrated the critical role of AAMP in angiogenesis and suggested blocking AAMP could serve as a potential therapeutic strategy for angiogenesis-related diseases.
Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), State and Local Joint Engineering Laboratory For Vascular Implants (Chongqing), Bioengineering College of Chongqing University, Chongqing, 400030, China.
Jianjun
J
Hu
Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), State and Local Joint Engineering Laboratory For Vascular Implants (Chongqing), Bioengineering College of Chongqing University, Chongqing, 400030, China.
Juhui
J
Qiu
Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), State and Local Joint Engineering Laboratory For Vascular Implants (Chongqing), Bioengineering College of Chongqing University, Chongqing, 400030, China.
Yiming
Y
Zheng
Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), State and Local Joint Engineering Laboratory For Vascular Implants (Chongqing), Bioengineering College of Chongqing University, Chongqing, 400030, China.
Tao
T
Zhang
Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), State and Local Joint Engineering Laboratory For Vascular Implants (Chongqing), Bioengineering College of Chongqing University, Chongqing, 400030, China.
Tieying
T
Yin
Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), State and Local Joint Engineering Laboratory For Vascular Implants (Chongqing), Bioengineering College of Chongqing University, Chongqing, 400030, China.
Xiang
X
Xie
Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), State and Local Joint Engineering Laboratory For Vascular Implants (Chongqing), Bioengineering College of Chongqing University, Chongqing, 400030, China. guixue_wang@126.com.
Guixue
G
Wang
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000378:metabolism; D002465:Cell Movement; D051606:G-Protein-Coupled Receptor Kinase 1 / Q000235:genetics / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D018919:Neovascularization, Physiologic; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
C093492:AAMP protein, human; D048868:Adaptor Proteins, Signal Transducing; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; C066737:RHOA protein, human; D051606:G-Protein-Coupled Receptor Kinase 1; C496764:GRK1 protein, human; C496765:Grk1 protein, rat; D020742:rhoA GTP-Binding Protein
Angio-associated migratory cell protein; Angiogenesis; Migration; RhoA/Rho kinase; Vascular endothelial growth factor