TGF-Beta Blockade Increases Renal Inflammation Caused by the C-Terminal Module of the CCN2. (5th May 2015)

• Record Type: Journal Article
• Authors: Rodrigues-Díez, Raquel; Rayego-Mateos, Sandra; Orejudo, Macarena; Aroeira, Luiz Stark; Selgas, Rafael; Ortiz, Alberto; Egido, Jesús; Ruiz-Ortega, Marta
• Other Names: Cantarini Luca Academic Editor.
• Is Part Of: Mediators of inflammation. Volume 2015(2015)
• Publication Date: 2015-05-05
• Subjects: Inflammation -- Mediators -- Periodicals; Biological response modifiers -- Periodicals; Inflammation (Pathologie) -- Médiateurs; Immunomodulateurs; Biological response modifiers; Inflammation -- Mediators; Immunology; Autacoids; Immunologic Factors; Cell Adhesion Molecules; Cell Communication; Cytokines; Inflammation; Periodicals; Electronic journals; 616.0473
• DOI: 10.1155/2015/506041
• Languages: English
• ISSNs: 0962-9351

Abstract

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.