title: TGF-Beta Blockade Increases Renal Inflammation Caused by the C-Terminal Module of the CCN2.
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.
authors.affiliation: Cellular Biology in Renal Diseases Laboratory, School of Medicine, Universidad Autónoma Madrid, 28040 Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Rodrigues-Díez
authors.affiliation: Cellular Biology in Renal Diseases Laboratory, School of Medicine, Universidad Autónoma Madrid, 28040 Madrid, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rayego-Mateos
authors.affiliation: Cellular Biology in Renal Diseases Laboratory, School of Medicine, Universidad Autónoma Madrid, 28040 Madrid, Spain.
authors.forename: Macarena
authors.initials: M
authors.lastname: Orejudo
authors.affiliation: Biomedical Research Center (CINBIO), Universidad De Vigo, 36282 Vigo, Spain.
authors.forename: Luiz Stark
authors.initials: LS
authors.lastname: Aroeira
authors.affiliation: Dialysis Unit, IDIPAZ, 28046 Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Selgas
authors.affiliation: Dialysis Unit, IIS-Fundación Jiménez Díaz, Autonoma University, 28040 Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
authors.affiliation: Renal and Vascular Laboratory, IIS-Fundación Jiménez Díaz, Autonoma University, 28040 Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
authors.affiliation: Cellular Biology in Renal Diseases Laboratory, School of Medicine, Universidad Autónoma Madrid, 28040 Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Ruiz-Ortega
mesh_terms: D000818:Animals; D055513:Connective Tissue Growth Factor / Q000633:toxicity*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D054390:Receptors, CCR2 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D054390:Receptors, CCR2; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor