Pronerve Growth Factor Induces Angiogenesis via Activation of TrkA: Possible Role in Proliferative Diabetic Retinopathy
Proliferative diabetic retinopathy (PDR) is the leading cause of blindness in working age Americans. We demonstrated that diabetes disturbs the homeostasis of nerve growth factor (NGF) resulting in accumulation of its precursor proNGF. Increases in proNGF were positively correlated with progression...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2013/432659 |
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| author | Sally L. Elshaer Mohammed A. Abdelsaid Ahmad Al-Azayzih Parag Kumar Suraporn Matragoon Julian J. Nussbaum Azza B. El-Remessy |
| author_facet | Sally L. Elshaer Mohammed A. Abdelsaid Ahmad Al-Azayzih Parag Kumar Suraporn Matragoon Julian J. Nussbaum Azza B. El-Remessy |
| author_sort | Sally L. Elshaer |
| collection | DOAJ |
| description | Proliferative diabetic retinopathy (PDR) is the leading cause of blindness in working age Americans. We demonstrated that diabetes disturbs the homeostasis of nerve growth factor (NGF) resulting in accumulation of its precursor proNGF. Increases in proNGF were positively correlated with progression of diabetic retinopathy, having the highest level in ocular fluids from PDR patients compared to nondiabetic patients. Here, we attempted to evaluate the contribution and the possible mechanism of proNGF to PDR. The angiogenic response of aqueous humor samples from PDR patients was examined in human retinal endothelial cells in the presence or absence of anti-proNGF antibody. Additional cultures were treated with mutant-proNGF in the presence of specific pharmacological inhibitors of TrkA and p75NTR receptors. PDR-aqueous humor samples exerted significant angiogenic response including cell proliferation, migration, and alignment into tube-like structures. These effects were significantly reduced by anti-proNGF antibody but not by IgG. Treatment of retinal endothelial cells with mutant-proNGF activated phosphorylation of TrkA and p38MAPK; however, it did not alter p75NTR expression. Inhibition of TrkA but not p75NTR significantly reduced mutant-proNGF-induced cell proliferation, cell migration, and tube formation. Taken together, these results provide evidence that proNGF can contribute to PDR at least in part via activation of TrkA. |
| format | Article |
| id | doaj-art-ae776a2b34d84b4d9c9a711663327628 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-ae776a2b34d84b4d9c9a7116633276282025-02-03T06:11:12ZengWileyJournal of Diabetes Research2314-67452314-67532013-01-01201310.1155/2013/432659432659Pronerve Growth Factor Induces Angiogenesis via Activation of TrkA: Possible Role in Proliferative Diabetic RetinopathySally L. Elshaer0Mohammed A. Abdelsaid1Ahmad Al-Azayzih2Parag Kumar3Suraporn Matragoon4Julian J. Nussbaum5Azza B. El-Remessy6Center for Pharmacy and Experimental Therapeutics, University of Georgia, 1120 15th Street HM-1200, Augusta, GA 30912, USACenter for Pharmacy and Experimental Therapeutics, University of Georgia, 1120 15th Street HM-1200, Augusta, GA 30912, USACenter for Pharmacy and Experimental Therapeutics, University of Georgia, 1120 15th Street HM-1200, Augusta, GA 30912, USACenter for Pharmacy and Experimental Therapeutics, University of Georgia, 1120 15th Street HM-1200, Augusta, GA 30912, USACenter for Pharmacy and Experimental Therapeutics, University of Georgia, 1120 15th Street HM-1200, Augusta, GA 30912, USACulver Vision Discovery Institute, Georgia Reagents University, Augusta, GA 30912, USACenter for Pharmacy and Experimental Therapeutics, University of Georgia, 1120 15th Street HM-1200, Augusta, GA 30912, USAProliferative diabetic retinopathy (PDR) is the leading cause of blindness in working age Americans. We demonstrated that diabetes disturbs the homeostasis of nerve growth factor (NGF) resulting in accumulation of its precursor proNGF. Increases in proNGF were positively correlated with progression of diabetic retinopathy, having the highest level in ocular fluids from PDR patients compared to nondiabetic patients. Here, we attempted to evaluate the contribution and the possible mechanism of proNGF to PDR. The angiogenic response of aqueous humor samples from PDR patients was examined in human retinal endothelial cells in the presence or absence of anti-proNGF antibody. Additional cultures were treated with mutant-proNGF in the presence of specific pharmacological inhibitors of TrkA and p75NTR receptors. PDR-aqueous humor samples exerted significant angiogenic response including cell proliferation, migration, and alignment into tube-like structures. These effects were significantly reduced by anti-proNGF antibody but not by IgG. Treatment of retinal endothelial cells with mutant-proNGF activated phosphorylation of TrkA and p38MAPK; however, it did not alter p75NTR expression. Inhibition of TrkA but not p75NTR significantly reduced mutant-proNGF-induced cell proliferation, cell migration, and tube formation. Taken together, these results provide evidence that proNGF can contribute to PDR at least in part via activation of TrkA.http://dx.doi.org/10.1155/2013/432659 |
| spellingShingle | Sally L. Elshaer Mohammed A. Abdelsaid Ahmad Al-Azayzih Parag Kumar Suraporn Matragoon Julian J. Nussbaum Azza B. El-Remessy Pronerve Growth Factor Induces Angiogenesis via Activation of TrkA: Possible Role in Proliferative Diabetic Retinopathy Journal of Diabetes Research |
| title | Pronerve Growth Factor Induces Angiogenesis via Activation of TrkA: Possible Role in Proliferative Diabetic Retinopathy |
| title_full | Pronerve Growth Factor Induces Angiogenesis via Activation of TrkA: Possible Role in Proliferative Diabetic Retinopathy |
| title_fullStr | Pronerve Growth Factor Induces Angiogenesis via Activation of TrkA: Possible Role in Proliferative Diabetic Retinopathy |
| title_full_unstemmed | Pronerve Growth Factor Induces Angiogenesis via Activation of TrkA: Possible Role in Proliferative Diabetic Retinopathy |
| title_short | Pronerve Growth Factor Induces Angiogenesis via Activation of TrkA: Possible Role in Proliferative Diabetic Retinopathy |
| title_sort | pronerve growth factor induces angiogenesis via activation of trka possible role in proliferative diabetic retinopathy |
| url | http://dx.doi.org/10.1155/2013/432659 |
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