1. TGF-Beta Blockade Increases Renal Inflammation Caused by the C-Terminal Module of the CCN2.
- Author
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Rodrigues-Díez, Raquel, Rayego-Mateos, Sandra, Orejudo, Macarena, Aroeira, Luiz Stark, Selgas, Rafael, Ortiz, Alberto, Egido, Jesús, and Ruiz-Ortega, Marta
- Subjects
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KIDNEY disease treatments , *TRANSFORMING growth factors-beta , *INFLAMMATION , *CONNECTIVE tissue growth factor , *BIOMARKERS , *CYTOKINES - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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