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MicroRNA-200b Regulates Vascular Endothelial Growth Factor–Mediated Alterations in Diabetic Retinopathy
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| Zeitschriftentitel: | Diabetes |
|---|---|
| Personen und Körperschaften: | , , , , |
| In: | Diabetes, 60, 2011, 4, S. 1314-1323 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Diabetes Association
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| Schlagwörter: |
| author_facet |
McArthur, Kara Feng, Biao Wu, Yuexiu Chen, Shali Chakrabarti, Subrata McArthur, Kara Feng, Biao Wu, Yuexiu Chen, Shali Chakrabarti, Subrata |
|---|---|
| author |
McArthur, Kara Feng, Biao Wu, Yuexiu Chen, Shali Chakrabarti, Subrata |
| spellingShingle |
McArthur, Kara Feng, Biao Wu, Yuexiu Chen, Shali Chakrabarti, Subrata Diabetes MicroRNA-200b Regulates Vascular Endothelial Growth Factor–Mediated Alterations in Diabetic Retinopathy Endocrinology, Diabetes and Metabolism Internal Medicine |
| author_sort |
mcarthur, kara |
| spelling |
McArthur, Kara Feng, Biao Wu, Yuexiu Chen, Shali Chakrabarti, Subrata 0012-1797 1939-327X American Diabetes Association Endocrinology, Diabetes and Metabolism Internal Medicine http://dx.doi.org/10.2337/db10-1557 <jats:sec> <jats:title>OBJECTIVE</jats:title> <jats:p>Diabetic retinopathy (DR) is a leading cause of blindness. Increased vascular endothelial growth factor (VEGF), promoting angiogenesis and increased permeability, is a key mechanistic abnormality in DR. We investigated microRNA (miRNA) alterations in DR with specific focus on miR-200b, and its downstream target, VEGF.</jats:p> </jats:sec> <jats:sec> <jats:title>RESEARCH DESIGN AND METHODS</jats:title> <jats:p>miRNA expression profiling microarray was used to examine the retinas of streptozotocin-induced diabetic rats. Expressions of specific miRNAs were verified with PCR in the rat retina and in glucose-exposed endothelial cells. A target search, based on sequence complementarities, identified specific targets. We analyzed mRNA levels and protein expression in endothelial cells from large vessels and retinal capillaries and in the rat retina, with or without injection of miR-200b mimic or antagomir. Localization of miR-200b and its functional analysis in the rat and human retinas were performed.</jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>Alteration of several miRNAs, including downregulation of miR-200b, were observed in the retina in diabetes. Such downregulation was validated in the retina of diabetic rats and in endothelial cells incubated in glucose. In parallel, VEGF (target of miR-200b) mRNA and protein were elevated. In the retina, miR-200b was localized in neuronal, glial, and vascular elements. Transfection of endothelial cells and intravitreal injection of miR-200b mimic prevented diabetes-induced increased VEGF mRNA and protein. Also prevented were glucose-induced increased permeability and angiogenesis. Furthermore, transfection of miR-200b antagonists (antagomir) led to increased VEGF production. Similar alterations were seen in the human retina.</jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>These studies show a novel mechanism involving miR-200b in DR. Identification of such mechanisms may lead to the development of novel miRNA-based therapy.</jats:p> </jats:sec> MicroRNA-200b Regulates Vascular Endothelial Growth Factor–Mediated Alterations in Diabetic Retinopathy Diabetes |
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10.2337/db10-1557 |
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Online Free |
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Medizin |
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American Diabetes Association, 2011 |
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American Diabetes Association, 2011 |
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0012-1797 1939-327X |
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0012-1797 1939-327X |
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2011 |
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American Diabetes Association |
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Diabetes |
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| title |
MicroRNA-200b Regulates Vascular Endothelial Growth Factor–Mediated Alterations in Diabetic Retinopathy |
| title_unstemmed |
MicroRNA-200b Regulates Vascular Endothelial Growth Factor–Mediated Alterations in Diabetic Retinopathy |
| title_full |
MicroRNA-200b Regulates Vascular Endothelial Growth Factor–Mediated Alterations in Diabetic Retinopathy |
| title_fullStr |
MicroRNA-200b Regulates Vascular Endothelial Growth Factor–Mediated Alterations in Diabetic Retinopathy |
| title_full_unstemmed |
MicroRNA-200b Regulates Vascular Endothelial Growth Factor–Mediated Alterations in Diabetic Retinopathy |
| title_short |
MicroRNA-200b Regulates Vascular Endothelial Growth Factor–Mediated Alterations in Diabetic Retinopathy |
| title_sort |
microrna-200b regulates vascular endothelial growth factor–mediated alterations in diabetic retinopathy |
| topic |
Endocrinology, Diabetes and Metabolism Internal Medicine |
| url |
http://dx.doi.org/10.2337/db10-1557 |
| publishDate |
2011 |
| physical |
1314-1323 |
| description |
<jats:sec>
<jats:title>OBJECTIVE</jats:title>
<jats:p>Diabetic retinopathy (DR) is a leading cause of blindness. Increased vascular endothelial growth factor (VEGF), promoting angiogenesis and increased permeability, is a key mechanistic abnormality in DR. We investigated microRNA (miRNA) alterations in DR with specific focus on miR-200b, and its downstream target, VEGF.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>RESEARCH DESIGN AND METHODS</jats:title>
<jats:p>miRNA expression profiling microarray was used to examine the retinas of streptozotocin-induced diabetic rats. Expressions of specific miRNAs were verified with PCR in the rat retina and in glucose-exposed endothelial cells. A target search, based on sequence complementarities, identified specific targets. We analyzed mRNA levels and protein expression in endothelial cells from large vessels and retinal capillaries and in the rat retina, with or without injection of miR-200b mimic or antagomir. Localization of miR-200b and its functional analysis in the rat and human retinas were performed.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>RESULTS</jats:title>
<jats:p>Alteration of several miRNAs, including downregulation of miR-200b, were observed in the retina in diabetes. Such downregulation was validated in the retina of diabetic rats and in endothelial cells incubated in glucose. In parallel, VEGF (target of miR-200b) mRNA and protein were elevated. In the retina, miR-200b was localized in neuronal, glial, and vascular elements. Transfection of endothelial cells and intravitreal injection of miR-200b mimic prevented diabetes-induced increased VEGF mRNA and protein. Also prevented were glucose-induced increased permeability and angiogenesis. Furthermore, transfection of miR-200b antagonists (antagomir) led to increased VEGF production. Similar alterations were seen in the human retina.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>CONCLUSIONS</jats:title>
<jats:p>These studies show a novel mechanism involving miR-200b in DR. Identification of such mechanisms may lead to the development of novel miRNA-based therapy.</jats:p>
</jats:sec> |
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| author | McArthur, Kara, Feng, Biao, Wu, Yuexiu, Chen, Shali, Chakrabarti, Subrata |
| author_facet | McArthur, Kara, Feng, Biao, Wu, Yuexiu, Chen, Shali, Chakrabarti, Subrata, McArthur, Kara, Feng, Biao, Wu, Yuexiu, Chen, Shali, Chakrabarti, Subrata |
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| description | <jats:sec> <jats:title>OBJECTIVE</jats:title> <jats:p>Diabetic retinopathy (DR) is a leading cause of blindness. Increased vascular endothelial growth factor (VEGF), promoting angiogenesis and increased permeability, is a key mechanistic abnormality in DR. We investigated microRNA (miRNA) alterations in DR with specific focus on miR-200b, and its downstream target, VEGF.</jats:p> </jats:sec> <jats:sec> <jats:title>RESEARCH DESIGN AND METHODS</jats:title> <jats:p>miRNA expression profiling microarray was used to examine the retinas of streptozotocin-induced diabetic rats. Expressions of specific miRNAs were verified with PCR in the rat retina and in glucose-exposed endothelial cells. A target search, based on sequence complementarities, identified specific targets. We analyzed mRNA levels and protein expression in endothelial cells from large vessels and retinal capillaries and in the rat retina, with or without injection of miR-200b mimic or antagomir. Localization of miR-200b and its functional analysis in the rat and human retinas were performed.</jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>Alteration of several miRNAs, including downregulation of miR-200b, were observed in the retina in diabetes. Such downregulation was validated in the retina of diabetic rats and in endothelial cells incubated in glucose. In parallel, VEGF (target of miR-200b) mRNA and protein were elevated. In the retina, miR-200b was localized in neuronal, glial, and vascular elements. Transfection of endothelial cells and intravitreal injection of miR-200b mimic prevented diabetes-induced increased VEGF mRNA and protein. Also prevented were glucose-induced increased permeability and angiogenesis. Furthermore, transfection of miR-200b antagonists (antagomir) led to increased VEGF production. Similar alterations were seen in the human retina.</jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>These studies show a novel mechanism involving miR-200b in DR. Identification of such mechanisms may lead to the development of novel miRNA-based therapy.</jats:p> </jats:sec> |
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| imprint | American Diabetes Association, 2011 |
| imprint_str_mv | American Diabetes Association, 2011 |
| institution | DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161 |
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| physical | 1314-1323 |
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| series | Diabetes |
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| spelling | McArthur, Kara Feng, Biao Wu, Yuexiu Chen, Shali Chakrabarti, Subrata 0012-1797 1939-327X American Diabetes Association Endocrinology, Diabetes and Metabolism Internal Medicine http://dx.doi.org/10.2337/db10-1557 <jats:sec> <jats:title>OBJECTIVE</jats:title> <jats:p>Diabetic retinopathy (DR) is a leading cause of blindness. Increased vascular endothelial growth factor (VEGF), promoting angiogenesis and increased permeability, is a key mechanistic abnormality in DR. We investigated microRNA (miRNA) alterations in DR with specific focus on miR-200b, and its downstream target, VEGF.</jats:p> </jats:sec> <jats:sec> <jats:title>RESEARCH DESIGN AND METHODS</jats:title> <jats:p>miRNA expression profiling microarray was used to examine the retinas of streptozotocin-induced diabetic rats. Expressions of specific miRNAs were verified with PCR in the rat retina and in glucose-exposed endothelial cells. A target search, based on sequence complementarities, identified specific targets. We analyzed mRNA levels and protein expression in endothelial cells from large vessels and retinal capillaries and in the rat retina, with or without injection of miR-200b mimic or antagomir. Localization of miR-200b and its functional analysis in the rat and human retinas were performed.</jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>Alteration of several miRNAs, including downregulation of miR-200b, were observed in the retina in diabetes. Such downregulation was validated in the retina of diabetic rats and in endothelial cells incubated in glucose. In parallel, VEGF (target of miR-200b) mRNA and protein were elevated. In the retina, miR-200b was localized in neuronal, glial, and vascular elements. Transfection of endothelial cells and intravitreal injection of miR-200b mimic prevented diabetes-induced increased VEGF mRNA and protein. Also prevented were glucose-induced increased permeability and angiogenesis. Furthermore, transfection of miR-200b antagonists (antagomir) led to increased VEGF production. Similar alterations were seen in the human retina.</jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>These studies show a novel mechanism involving miR-200b in DR. Identification of such mechanisms may lead to the development of novel miRNA-based therapy.</jats:p> </jats:sec> MicroRNA-200b Regulates Vascular Endothelial Growth Factor–Mediated Alterations in Diabetic Retinopathy Diabetes |
| spellingShingle | McArthur, Kara, Feng, Biao, Wu, Yuexiu, Chen, Shali, Chakrabarti, Subrata, Diabetes, MicroRNA-200b Regulates Vascular Endothelial Growth Factor–Mediated Alterations in Diabetic Retinopathy, Endocrinology, Diabetes and Metabolism, Internal Medicine |
| title | MicroRNA-200b Regulates Vascular Endothelial Growth Factor–Mediated Alterations in Diabetic Retinopathy |
| title_full | MicroRNA-200b Regulates Vascular Endothelial Growth Factor–Mediated Alterations in Diabetic Retinopathy |
| title_fullStr | MicroRNA-200b Regulates Vascular Endothelial Growth Factor–Mediated Alterations in Diabetic Retinopathy |
| title_full_unstemmed | MicroRNA-200b Regulates Vascular Endothelial Growth Factor–Mediated Alterations in Diabetic Retinopathy |
| title_short | MicroRNA-200b Regulates Vascular Endothelial Growth Factor–Mediated Alterations in Diabetic Retinopathy |
| title_sort | microrna-200b regulates vascular endothelial growth factor–mediated alterations in diabetic retinopathy |
| title_unstemmed | MicroRNA-200b Regulates Vascular Endothelial Growth Factor–Mediated Alterations in Diabetic Retinopathy |
| topic | Endocrinology, Diabetes and Metabolism, Internal Medicine |
| url | http://dx.doi.org/10.2337/db10-1557 |