TGF-Beta Blockade Increases Renal Inflammation Caused by the C-Terminal Module of the CCN2
The CCN family member 2 (CCN2, also known as connective tissue growth factor) may behave as a risk biomarker and a potential therapeutic target for renal disease. CCN2 participates in the regulation of inflammation and fibrosis. TGF-β is considered...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2015-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2015/506041 |
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| author | Raquel Rodrigues-Díez Sandra Rayego-Mateos Macarena Orejudo Luiz Stark Aroeira Rafael Selgas Alberto Ortiz Jesús Egido Marta Ruiz-Ortega |
| author_facet | Raquel Rodrigues-Díez Sandra Rayego-Mateos Macarena Orejudo Luiz Stark Aroeira Rafael Selgas Alberto Ortiz Jesús Egido Marta Ruiz-Ortega |
| author_sort | Raquel Rodrigues-Díez |
| collection | DOAJ |
| description | The CCN family member 2 (CCN2, also known as
connective tissue growth factor) may behave as a risk
biomarker and a potential therapeutic target for renal
disease. CCN2 participates in the regulation of
inflammation and fibrosis. TGF-β is considered
the main fibrogenic cytokine; however, in some
pathological settings TGF-β also has
anti-inflammatory properties. CCN2 has been proposed
as a downstream profibrotic mediator of TGF-β,
but data on TGF-β role in CCN2 actions are
scarce. Our aim was to evaluate the effect of
TGF-β blockade in CCN2-mediated experimental
renal damage. Systemic administration of the
C-terminal module of CCN2 to mice caused sustained
renal inflammation. In these mice, TGF-β
blockade, using an anti-TGF-β neutralizing
antibody, significantly increased renal expression of
the NGAL (a kidney injury biomarker), kidney
infiltration by monocytes/macrophages, and
upregulation of MCP-1 expression. The
anti-inflammatory effect of TGF-β seems to be
mediated by a dysregulation of the systemic Treg
immune response, shown by decreased levels of
circulating CD4+/Foxp3+Treg
cells. Our experimental data support the idea that
TGF-β exerts anti-inflammatory actions in the
kidney and suggest that it is not an optimal
therapeutic target. |
| format | Article |
| id | doaj-art-d2b522f8da0244cfa98f123dd1f93058 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-d2b522f8da0244cfa98f123dd1f930582025-08-20T03:24:07ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/506041506041TGF-Beta Blockade Increases Renal Inflammation Caused by the C-Terminal Module of the CCN2Raquel Rodrigues-Díez0Sandra Rayego-Mateos1Macarena Orejudo2Luiz Stark Aroeira3Rafael Selgas4Alberto Ortiz5Jesús Egido6Marta Ruiz-Ortega7Cellular Biology in Renal Diseases Laboratory, School of Medicine, Universidad Autónoma Madrid, 28040 Madrid, SpainCellular Biology in Renal Diseases Laboratory, School of Medicine, Universidad Autónoma Madrid, 28040 Madrid, SpainCellular Biology in Renal Diseases Laboratory, School of Medicine, Universidad Autónoma Madrid, 28040 Madrid, SpainBiomedical Research Center (CINBIO), Universidad De Vigo, 36282 Vigo, SpainDialysis Unit, IDIPAZ, 28046 Madrid, SpainDialysis Unit, IIS-Fundación Jiménez Díaz, Autonoma University, 28040 Madrid, SpainRenal and Vascular Laboratory, IIS-Fundación Jiménez Díaz, Autonoma University, 28040 Madrid, SpainCellular Biology in Renal Diseases Laboratory, School of Medicine, Universidad Autónoma Madrid, 28040 Madrid, SpainThe CCN family member 2 (CCN2, also known as connective tissue growth factor) may behave as a risk biomarker and a potential therapeutic target for renal disease. CCN2 participates in the regulation of inflammation and fibrosis. TGF-β is considered the main fibrogenic cytokine; however, in some pathological settings TGF-β also has anti-inflammatory properties. CCN2 has been proposed as a downstream profibrotic mediator of TGF-β, but data on TGF-β role in CCN2 actions are scarce. Our aim was to evaluate the effect of TGF-β blockade in CCN2-mediated experimental renal damage. Systemic administration of the C-terminal module of CCN2 to mice caused sustained renal inflammation. In these mice, TGF-β blockade, using an anti-TGF-β neutralizing antibody, significantly increased renal expression of the NGAL (a kidney injury biomarker), kidney infiltration by monocytes/macrophages, and upregulation of MCP-1 expression. The anti-inflammatory effect of TGF-β seems to be mediated by a dysregulation of the systemic Treg immune response, shown by decreased levels of circulating CD4+/Foxp3+Treg cells. Our experimental data support the idea that TGF-β exerts anti-inflammatory actions in the kidney and suggest that it is not an optimal therapeutic target.http://dx.doi.org/10.1155/2015/506041 |
| spellingShingle | Raquel Rodrigues-Díez Sandra Rayego-Mateos Macarena Orejudo Luiz Stark Aroeira Rafael Selgas Alberto Ortiz Jesús Egido Marta Ruiz-Ortega TGF-Beta Blockade Increases Renal Inflammation Caused by the C-Terminal Module of the CCN2 Mediators of Inflammation |
| title | TGF-Beta Blockade Increases Renal Inflammation Caused by the C-Terminal Module of the CCN2 |
| title_full | TGF-Beta Blockade Increases Renal Inflammation Caused by the C-Terminal Module of the CCN2 |
| title_fullStr | TGF-Beta Blockade Increases Renal Inflammation Caused by the C-Terminal Module of the CCN2 |
| title_full_unstemmed | TGF-Beta Blockade Increases Renal Inflammation Caused by the C-Terminal Module of the CCN2 |
| title_short | TGF-Beta Blockade Increases Renal Inflammation Caused by the C-Terminal Module of the CCN2 |
| title_sort | tgf beta blockade increases renal inflammation caused by the c terminal module of the ccn2 |
| url | http://dx.doi.org/10.1155/2015/506041 |
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