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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.

Author information

1
Cellular Biology in Renal Diseases Laboratory, School of Medicine, Universidad Autónoma Madrid, 28040 Madrid, Spain.
2
Biomedical Research Center (CINBIO), Universidad De Vigo, 36282 Vigo, Spain.
3
Dialysis Unit, IDIPAZ, 28046 Madrid, Spain.
4
Dialysis Unit, IIS-Fundación Jiménez Díaz, Autonoma University, 28040 Madrid, Spain.
5
Renal and Vascular Laboratory, IIS-Fundación Jiménez Díaz, Autonoma University, 28040 Madrid, Spain.

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.

PMID:
26074680
PMCID:
PMC4436472
DOI:
10.1155/2015/506041
[Indexed for MEDLINE]
Free PMC Article

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