CD82 restrains pathological Angiogenesis by altering lipid raft clustering and CD44 trafficking in endothelial cells

Quan Wei, Feng Zhang, Mekel M. Richardson, Nathan H. Roy, William Rodgers, Yuechueng Liu, Wenyuan Zhao, Chenying Fu, Yingjun Ding, Chao Huang, Yuanjian Chen, Yao Sun, Lexi Ding, Yang Hu, Jian Xing Ma, Michael E. Boulton, Satish Pasula, Jonathan D. Wren, Satoshi Tanaka, Xiaolin HuangMarkus Thali, Günter J. Hämmerling, Xin A. Zhang

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1493-1504
Number of pages12
JournalCirculation
Volume130
Issue number17
DOIs
StatePublished - 2014

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Pathologic Neovascularization
Cluster Analysis
Endothelial Cells
Null Lymphocytes
Lipids
Gangliosides
Cell Adhesion Molecules
Membrane Microdomains
Clathrin
Pathologic Processes
Endocytosis
Morphogenesis
Integrins
Membrane Potentials
Cell Movement
Cell Membrane
Neoplasms
Proteins

Keywords

  • Cell movement
  • Endocytosis
  • Membrane microdomains
  • Neovascularization
  • Pathological

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

Wei, Q., Zhang, F., Richardson, M. M., Roy, N. H., Rodgers, W., Liu, Y., ... Zhang, X. A. (2014). CD82 restrains pathological Angiogenesis by altering lipid raft clustering and CD44 trafficking in endothelial cells. Circulation, 130(17), 1493-1504. https://doi.org/10.1161/CIRCULATIONAHA.114.011096

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 journalArticle

Wei, Q, Zhang, F, Richardson, MM, Roy, NH, Rodgers, W, Liu, Y, Zhao, W, Fu, C, Ding, Y, Huang, C, Chen, Y, Sun, Y, Ding, L, Hu, Y, Ma, JX, Boulton, ME, Pasula, S, Wren, JD, Tanaka, S, Huang, X, Thali, M, Hämmerling, GJ & Zhang, XA 2014, 'CD82 restrains pathological Angiogenesis by altering lipid raft clustering and CD44 trafficking in endothelial cells', Circulation, vol. 130, no. 17, pp. 1493-1504. https://doi.org/10.1161/CIRCULATIONAHA.114.011096
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. / CD82 restrains pathological Angiogenesis by altering lipid raft clustering and CD44 trafficking in endothelial cells. In: Circulation. 2014 ; Vol. 130, No. 17. pp. 1493-1504.
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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.",
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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.

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