Abstract
Background: Angiogenesis is crucial for many pathological processes and becomes a therapeutic strategy against diseases ranging from infammation to cancer. The regulatory mechanism of angiogenesis remains unclear. Although tetraspanin CD82 is widely expressed in various endothelial cells (ECs), its vascular function is unknown. Methods and Results: Angiogenesis was examined in Cd82-null mice with in vivo and ex vivo morphogenesis assays. Cellular functions, molecular interactions, and signaling were analyzed in Cd82-null ECs. Angiogenic responses to various stimuli became markedly increased upon Cd82 ablation. Major changes in Cd82-null ECs were enhanced migration and invasion, likely resulting from the upregulated expression of cell adhesion molecules such as CD44 and integrins at the cell surface and subsequently elevated outside-in signaling. Gangliosides, lipid raft clustering, and CD44-membrane microdomain interactions were increased in the plasma membrane of Cd82-null ECs, leading to less clathrin-independent endocytosis and then more surface presence of CD44. Conclusions: Our study reveals that CD82 restrains pathological angiogenesis by inhibiting EC movement, that lipid raft clustering and cell adhesion molecule trafficking modulate angiogenic potential, that transmembrane protein modulates lipid rafts, and that the perturbation of CD82-ganglioside-CD44 signaling attenuates pathological angiogenesis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1493-1504 |
| Number of pages | 12 |
| Journal | Circulation |
| Volume | 130 |
| Issue number | 17 |
| DOIs | |
| State | Published - 2014 |
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Keywords
- Cell movement
- Endocytosis
- Membrane microdomains
- Neovascularization
- Pathological
ASJC Scopus subject areas
- Physiology (medical)
- Cardiology and Cardiovascular Medicine
- Medicine(all)
Cite this
CD82 restrains pathological Angiogenesis by altering lipid raft clustering and CD44 trafficking in endothelial cells. / Wei, Quan; Zhang, Feng; Richardson, Mekel M.; Roy, Nathan H.; Rodgers, William; Liu, Yuechueng; Zhao, Wenyuan; Fu, Chenying; Ding, Yingjun; Huang, Chao; Chen, Yuanjian; Sun, Yao; Ding, Lexi; Hu, Yang; Ma, Jian Xing; Boulton, Michael E.; Pasula, Satish; Wren, Jonathan D.; Tanaka, Satoshi; Huang, Xiaolin; Thali, Markus; Hämmerling, Günter J.; Zhang, Xin A.
In: Circulation, Vol. 130, No. 17, 2014, p. 1493-1504.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CD82 restrains pathological Angiogenesis by altering lipid raft clustering and CD44 trafficking in endothelial cells
AU - Wei, Quan
AU - Zhang, Feng
AU - Richardson, Mekel M.
AU - Roy, Nathan H.
AU - Rodgers, William
AU - Liu, Yuechueng
AU - Zhao, Wenyuan
AU - Fu, Chenying
AU - Ding, Yingjun
AU - Huang, Chao
AU - Chen, Yuanjian
AU - Sun, Yao
AU - Ding, Lexi
AU - Hu, Yang
AU - Ma, Jian Xing
AU - Boulton, Michael E.
AU - Pasula, Satish
AU - Wren, Jonathan D.
AU - Tanaka, Satoshi
AU - Huang, Xiaolin
AU - Thali, Markus
AU - Hämmerling, Günter J.
AU - Zhang, Xin A.
PY - 2014
Y1 - 2014
N2 - Background: Angiogenesis is crucial for many pathological processes and becomes a therapeutic strategy against diseases ranging from infammation to cancer. The regulatory mechanism of angiogenesis remains unclear. Although tetraspanin CD82 is widely expressed in various endothelial cells (ECs), its vascular function is unknown. Methods and Results: Angiogenesis was examined in Cd82-null mice with in vivo and ex vivo morphogenesis assays. Cellular functions, molecular interactions, and signaling were analyzed in Cd82-null ECs. Angiogenic responses to various stimuli became markedly increased upon Cd82 ablation. Major changes in Cd82-null ECs were enhanced migration and invasion, likely resulting from the upregulated expression of cell adhesion molecules such as CD44 and integrins at the cell surface and subsequently elevated outside-in signaling. Gangliosides, lipid raft clustering, and CD44-membrane microdomain interactions were increased in the plasma membrane of Cd82-null ECs, leading to less clathrin-independent endocytosis and then more surface presence of CD44. Conclusions: Our study reveals that CD82 restrains pathological angiogenesis by inhibiting EC movement, that lipid raft clustering and cell adhesion molecule trafficking modulate angiogenic potential, that transmembrane protein modulates lipid rafts, and that the perturbation of CD82-ganglioside-CD44 signaling attenuates pathological angiogenesis.
AB - Background: Angiogenesis is crucial for many pathological processes and becomes a therapeutic strategy against diseases ranging from infammation to cancer. The regulatory mechanism of angiogenesis remains unclear. Although tetraspanin CD82 is widely expressed in various endothelial cells (ECs), its vascular function is unknown. Methods and Results: Angiogenesis was examined in Cd82-null mice with in vivo and ex vivo morphogenesis assays. Cellular functions, molecular interactions, and signaling were analyzed in Cd82-null ECs. Angiogenic responses to various stimuli became markedly increased upon Cd82 ablation. Major changes in Cd82-null ECs were enhanced migration and invasion, likely resulting from the upregulated expression of cell adhesion molecules such as CD44 and integrins at the cell surface and subsequently elevated outside-in signaling. Gangliosides, lipid raft clustering, and CD44-membrane microdomain interactions were increased in the plasma membrane of Cd82-null ECs, leading to less clathrin-independent endocytosis and then more surface presence of CD44. Conclusions: Our study reveals that CD82 restrains pathological angiogenesis by inhibiting EC movement, that lipid raft clustering and cell adhesion molecule trafficking modulate angiogenic potential, that transmembrane protein modulates lipid rafts, and that the perturbation of CD82-ganglioside-CD44 signaling attenuates pathological angiogenesis.
KW - Cell movement
KW - Endocytosis
KW - Membrane microdomains
KW - Neovascularization
KW - Pathological
UR - http://www.scopus.com/inward/record.url?scp=84922010313&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84922010313&partnerID=8YFLogxK
U2 - 10.1161/CIRCULATIONAHA.114.011096
DO - 10.1161/CIRCULATIONAHA.114.011096
M3 - Article
C2 - 25149363
AN - SCOPUS:84922010313
VL - 130
SP - 1493
EP - 1504
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 17
ER -