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

Abstract EN

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.