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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| Summary: | 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. |
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| ISSN: | 0962-9351 1466-1861 |