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Mediators Inflamm. 2015;2015:506041. doi: 10.1155/2015/506041. Epub 2015 May 5.

TGF-Beta Blockade Increases Renal Inflammation Caused by the C-Terminal Module of the CCN2.

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Cellular Biology in Renal Diseases Laboratory, School of Medicine, Universidad Autónoma Madrid, 28040 Madrid, Spain.
Biomedical Research Center (CINBIO), Universidad De Vigo, 36282 Vigo, Spain.
Dialysis Unit, IDIPAZ, 28046 Madrid, Spain.
Dialysis Unit, IIS-Fundación Jiménez Díaz, Autonoma University, 28040 Madrid, Spain.
Renal and Vascular Laboratory, IIS-Fundación Jiménez Díaz, Autonoma University, 28040 Madrid, Spain.


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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