Abstract
Purpose. The angiopoietin (Ang) system plays an important role in vascular stabilization and pathologic neovascularization. The hypothesis for the study was that, in addition to modulating endothelial cell behavior, the angiopoietin/Tie-2 system also regulates the pericyte apoptosis and/or the vessel maturation associated with diabetic retinopathy. methods. Tie-2 expression in cultured retinal pericytes was analyzed by using ELISA, Western Blot analysis, and flow cytometry. CD13 (aminopeptidase N) expression in pericytes was determined by Western blot analysis and Ang effects verified with Tie-2 antisense treatment. Cell proliferation was monitored by crystal violet uptake, and pericyte migration was assessed in a scrape wound. Annexin V-FITC flow cytometry was used to quantify pericyte apoptosis. Results. Pericytes expressed a functionally active Tie-2 receptor upregulated by both Ang-1 and -2 (P <0.05). In pericytes undergoing apoptosis induced by either TNF-α or high glucose Ang-1 increased survival (P <0.05 for TNF-α P <0.01 for high glucose), whereas Ang-2 increased apoptosis. Ang-1 enhanced CD13 expression in a dose-dependent manner (P <0.05) and stimulated pericyte migration in a synthetic matrix wound- healing assay that was associated with a change in F-actin organization. Addition of Tie-2 antisense confirmed that angio- poietins act through Tie-2. onclusions. These findings demonstrate that Tie-2 is functional in pericytes and may play an important role in the progression of diabetic retinopathy, by regulating pericyte loss and influencing the activation state and recruitment of pericytes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2163-2171 |
| Number of pages | 9 |
| Journal | Investigative Ophthalmology and Visual Science |
| Volume | 49 |
| Issue number | 5 |
| DOIs | |
| State | Published - Apr 2008 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Ophthalmology
- Sensory Systems
- Cellular and Molecular Neuroscience
Cite this
The angiopoietin/Tie-2 system regulates pericyte survival and recruitment in diabetic retinopathy. / Cai, Jun; Kehoe, Oksana; Smith, Gill M.; Hykin, Philip; Boulton, Michael E.
In: Investigative Ophthalmology and Visual Science, Vol. 49, No. 5, 04.2008, p. 2163-2171.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The angiopoietin/Tie-2 system regulates pericyte survival and recruitment in diabetic retinopathy
AU - Cai, Jun
AU - Kehoe, Oksana
AU - Smith, Gill M.
AU - Hykin, Philip
AU - Boulton, Michael E.
PY - 2008/4
Y1 - 2008/4
N2 - Purpose. The angiopoietin (Ang) system plays an important role in vascular stabilization and pathologic neovascularization. The hypothesis for the study was that, in addition to modulating endothelial cell behavior, the angiopoietin/Tie-2 system also regulates the pericyte apoptosis and/or the vessel maturation associated with diabetic retinopathy. methods. Tie-2 expression in cultured retinal pericytes was analyzed by using ELISA, Western Blot analysis, and flow cytometry. CD13 (aminopeptidase N) expression in pericytes was determined by Western blot analysis and Ang effects verified with Tie-2 antisense treatment. Cell proliferation was monitored by crystal violet uptake, and pericyte migration was assessed in a scrape wound. Annexin V-FITC flow cytometry was used to quantify pericyte apoptosis. Results. Pericytes expressed a functionally active Tie-2 receptor upregulated by both Ang-1 and -2 (P <0.05). In pericytes undergoing apoptosis induced by either TNF-α or high glucose Ang-1 increased survival (P <0.05 for TNF-α P <0.01 for high glucose), whereas Ang-2 increased apoptosis. Ang-1 enhanced CD13 expression in a dose-dependent manner (P <0.05) and stimulated pericyte migration in a synthetic matrix wound- healing assay that was associated with a change in F-actin organization. Addition of Tie-2 antisense confirmed that angio- poietins act through Tie-2. onclusions. These findings demonstrate that Tie-2 is functional in pericytes and may play an important role in the progression of diabetic retinopathy, by regulating pericyte loss and influencing the activation state and recruitment of pericytes.
AB - Purpose. The angiopoietin (Ang) system plays an important role in vascular stabilization and pathologic neovascularization. The hypothesis for the study was that, in addition to modulating endothelial cell behavior, the angiopoietin/Tie-2 system also regulates the pericyte apoptosis and/or the vessel maturation associated with diabetic retinopathy. methods. Tie-2 expression in cultured retinal pericytes was analyzed by using ELISA, Western Blot analysis, and flow cytometry. CD13 (aminopeptidase N) expression in pericytes was determined by Western blot analysis and Ang effects verified with Tie-2 antisense treatment. Cell proliferation was monitored by crystal violet uptake, and pericyte migration was assessed in a scrape wound. Annexin V-FITC flow cytometry was used to quantify pericyte apoptosis. Results. Pericytes expressed a functionally active Tie-2 receptor upregulated by both Ang-1 and -2 (P <0.05). In pericytes undergoing apoptosis induced by either TNF-α or high glucose Ang-1 increased survival (P <0.05 for TNF-α P <0.01 for high glucose), whereas Ang-2 increased apoptosis. Ang-1 enhanced CD13 expression in a dose-dependent manner (P <0.05) and stimulated pericyte migration in a synthetic matrix wound- healing assay that was associated with a change in F-actin organization. Addition of Tie-2 antisense confirmed that angio- poietins act through Tie-2. onclusions. These findings demonstrate that Tie-2 is functional in pericytes and may play an important role in the progression of diabetic retinopathy, by regulating pericyte loss and influencing the activation state and recruitment of pericytes.
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UR - http://www.scopus.com/inward/citedby.url?scp=44649189401&partnerID=8YFLogxK
U2 - 10.1167/iovs.07-1206
DO - 10.1167/iovs.07-1206
M3 - Article
C2 - 18436850
AN - SCOPUS:44649189401
VL - 49
SP - 2163
EP - 2171
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 5
ER -