Effects of tenascin-C on normal and diabetic retinal endothelial cells in culture

Raquel Castellon, Sergio Caballero, Hamdi K. Hamdi, Shari R. Atilano, Annette M. Aoki, Roy W. Tarnuzzer, M. Cristina Kenney, Maria B. Grant, Alexander V. Ljubimov

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Abstract

PURPOSE. Tenascin-C (TN-C) is expressed in embryogenesis, tissue remodeling, and healing. It is up-regulated in retinas of patients affected by diabetic retinopathy (DR). Because TN-C may promote neovascularization, its potential angiogenic effects were examined in vitro in normal and diabetic retinal endothelial cells (RECs). METHODS. Bovine and human RECs were cultured on plastic or reconstituted basement membrane (BM) matrix. Production of TN-C, capillary-like tube formation, secondary sprouting, and cell migration, survival, and proliferation were measured with or without angiogenic growth factors (GFs). Antibodies and inhibitors were used to determine the involvement of specific TN-C receptors and signaling pathways. RESULTS. TN-C significantly delayed collapse of REC capillary-like tubes on BM matrix. It decreased tube involution associated with serum deprivation, high glucose, and exposure to TGF-β. TN-C's enhancement of tube stability was mediated by αvβ3 integrin. TN-C increased REC viability in 0.5% serum and stimulated REC proliferation in 10% serum. It promoted REC secondary sprouting on BM matrix, which involved signaling through mitogen-activated kinase kinase (MEK) and p38 mitogen-activated protein kinase. TN-C also enhanced tube branching after treatment with VEGF and stimulated REC migration twofold. Angiogenic GF increased TN-C production by RECs in an additive manner, which may explain higher levels of TN-C deposition in DR cells. CONCLUSIONS. TN-C was overexpressed in diabetic and DR REC cultures. TN-C enhanced the sprouting, migratory, and survival effects of angiogenic GFs, and had distinct proliferative, migratory, and protective capacities. The data suggest that TN-C may act as a proangiogenic mediator in DR and other pathologic conditions involving neovascularization.

Original languageEnglish (US)
Pages (from-to)2758-2766
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume43
Issue number8
StatePublished - 2002
Externally publishedYes

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Tenascin
Endothelial Cells
Cell Culture Techniques
Diabetic Retinopathy
Angiogenesis Inducing Agents
Basement Membrane
Intercellular Signaling Peptides and Proteins
Cell Movement
Cell Survival
Serum
Cell Proliferation
MAP Kinase Kinase Kinases
p38 Mitogen-Activated Protein Kinases
Mitogens
Integrins
Vascular Endothelial Growth Factor A
Plastics
Embryonic Development
Retina

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Castellon, R., Caballero, S., Hamdi, H. K., Atilano, S. R., Aoki, A. M., Tarnuzzer, R. W., ... Ljubimov, A. V. (2002). Effects of tenascin-C on normal and diabetic retinal endothelial cells in culture. Investigative Ophthalmology and Visual Science, 43(8), 2758-2766.

Effects of tenascin-C on normal and diabetic retinal endothelial cells in culture. / Castellon, Raquel; Caballero, Sergio; Hamdi, Hamdi K.; Atilano, Shari R.; Aoki, Annette M.; Tarnuzzer, Roy W.; Kenney, M. Cristina; Grant, Maria B.; Ljubimov, Alexander V.

In: Investigative Ophthalmology and Visual Science, Vol. 43, No. 8, 2002, p. 2758-2766.

Research output: Contribution to journalArticle

Castellon, R, Caballero, S, Hamdi, HK, Atilano, SR, Aoki, AM, Tarnuzzer, RW, Kenney, MC, Grant, MB & Ljubimov, AV 2002, 'Effects of tenascin-C on normal and diabetic retinal endothelial cells in culture', Investigative Ophthalmology and Visual Science, vol. 43, no. 8, pp. 2758-2766.
Castellon R, Caballero S, Hamdi HK, Atilano SR, Aoki AM, Tarnuzzer RW et al. Effects of tenascin-C on normal and diabetic retinal endothelial cells in culture. Investigative Ophthalmology and Visual Science. 2002;43(8):2758-2766.
Castellon, Raquel ; Caballero, Sergio ; Hamdi, Hamdi K. ; Atilano, Shari R. ; Aoki, Annette M. ; Tarnuzzer, Roy W. ; Kenney, M. Cristina ; Grant, Maria B. ; Ljubimov, Alexander V. / Effects of tenascin-C on normal and diabetic retinal endothelial cells in culture. In: Investigative Ophthalmology and Visual Science. 2002 ; Vol. 43, No. 8. pp. 2758-2766.
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abstract = "PURPOSE. Tenascin-C (TN-C) is expressed in embryogenesis, tissue remodeling, and healing. It is up-regulated in retinas of patients affected by diabetic retinopathy (DR). Because TN-C may promote neovascularization, its potential angiogenic effects were examined in vitro in normal and diabetic retinal endothelial cells (RECs). METHODS. Bovine and human RECs were cultured on plastic or reconstituted basement membrane (BM) matrix. Production of TN-C, capillary-like tube formation, secondary sprouting, and cell migration, survival, and proliferation were measured with or without angiogenic growth factors (GFs). Antibodies and inhibitors were used to determine the involvement of specific TN-C receptors and signaling pathways. RESULTS. TN-C significantly delayed collapse of REC capillary-like tubes on BM matrix. It decreased tube involution associated with serum deprivation, high glucose, and exposure to TGF-β. TN-C's enhancement of tube stability was mediated by αvβ3 integrin. TN-C increased REC viability in 0.5{\%} serum and stimulated REC proliferation in 10{\%} serum. It promoted REC secondary sprouting on BM matrix, which involved signaling through mitogen-activated kinase kinase (MEK) and p38 mitogen-activated protein kinase. TN-C also enhanced tube branching after treatment with VEGF and stimulated REC migration twofold. Angiogenic GF increased TN-C production by RECs in an additive manner, which may explain higher levels of TN-C deposition in DR cells. CONCLUSIONS. TN-C was overexpressed in diabetic and DR REC cultures. TN-C enhanced the sprouting, migratory, and survival effects of angiogenic GFs, and had distinct proliferative, migratory, and protective capacities. The data suggest that TN-C may act as a proangiogenic mediator in DR and other pathologic conditions involving neovascularization.",
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T1 - Effects of tenascin-C on normal and diabetic retinal endothelial cells in culture

AU - Castellon, Raquel

AU - Caballero, Sergio

AU - Hamdi, Hamdi K.

AU - Atilano, Shari R.

AU - Aoki, Annette M.

AU - Tarnuzzer, Roy W.

AU - Kenney, M. Cristina

AU - Grant, Maria B.

AU - Ljubimov, Alexander V.

PY - 2002

Y1 - 2002

N2 - PURPOSE. Tenascin-C (TN-C) is expressed in embryogenesis, tissue remodeling, and healing. It is up-regulated in retinas of patients affected by diabetic retinopathy (DR). Because TN-C may promote neovascularization, its potential angiogenic effects were examined in vitro in normal and diabetic retinal endothelial cells (RECs). METHODS. Bovine and human RECs were cultured on plastic or reconstituted basement membrane (BM) matrix. Production of TN-C, capillary-like tube formation, secondary sprouting, and cell migration, survival, and proliferation were measured with or without angiogenic growth factors (GFs). Antibodies and inhibitors were used to determine the involvement of specific TN-C receptors and signaling pathways. RESULTS. TN-C significantly delayed collapse of REC capillary-like tubes on BM matrix. It decreased tube involution associated with serum deprivation, high glucose, and exposure to TGF-β. TN-C's enhancement of tube stability was mediated by αvβ3 integrin. TN-C increased REC viability in 0.5% serum and stimulated REC proliferation in 10% serum. It promoted REC secondary sprouting on BM matrix, which involved signaling through mitogen-activated kinase kinase (MEK) and p38 mitogen-activated protein kinase. TN-C also enhanced tube branching after treatment with VEGF and stimulated REC migration twofold. Angiogenic GF increased TN-C production by RECs in an additive manner, which may explain higher levels of TN-C deposition in DR cells. CONCLUSIONS. TN-C was overexpressed in diabetic and DR REC cultures. TN-C enhanced the sprouting, migratory, and survival effects of angiogenic GFs, and had distinct proliferative, migratory, and protective capacities. The data suggest that TN-C may act as a proangiogenic mediator in DR and other pathologic conditions involving neovascularization.

AB - PURPOSE. Tenascin-C (TN-C) is expressed in embryogenesis, tissue remodeling, and healing. It is up-regulated in retinas of patients affected by diabetic retinopathy (DR). Because TN-C may promote neovascularization, its potential angiogenic effects were examined in vitro in normal and diabetic retinal endothelial cells (RECs). METHODS. Bovine and human RECs were cultured on plastic or reconstituted basement membrane (BM) matrix. Production of TN-C, capillary-like tube formation, secondary sprouting, and cell migration, survival, and proliferation were measured with or without angiogenic growth factors (GFs). Antibodies and inhibitors were used to determine the involvement of specific TN-C receptors and signaling pathways. RESULTS. TN-C significantly delayed collapse of REC capillary-like tubes on BM matrix. It decreased tube involution associated with serum deprivation, high glucose, and exposure to TGF-β. TN-C's enhancement of tube stability was mediated by αvβ3 integrin. TN-C increased REC viability in 0.5% serum and stimulated REC proliferation in 10% serum. It promoted REC secondary sprouting on BM matrix, which involved signaling through mitogen-activated kinase kinase (MEK) and p38 mitogen-activated protein kinase. TN-C also enhanced tube branching after treatment with VEGF and stimulated REC migration twofold. Angiogenic GF increased TN-C production by RECs in an additive manner, which may explain higher levels of TN-C deposition in DR cells. CONCLUSIONS. TN-C was overexpressed in diabetic and DR REC cultures. TN-C enhanced the sprouting, migratory, and survival effects of angiogenic GFs, and had distinct proliferative, migratory, and protective capacities. The data suggest that TN-C may act as a proangiogenic mediator in DR and other pathologic conditions involving neovascularization.

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C2 - 12147613

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