2008 JASN IMPACT FACTOR 7.505	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2008090999v1 20/7/1513    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Sánchez-López, E. Articles by Ruiz-Ortega, M. PubMed PubMed Citation Articles by Sánchez-López, E. Articles by Ruiz-Ortega, M.

CTGF Promotes Inflammatory Cell Infiltration of the Renal Interstitium by Activating NF-B

Elsa Sánchez-López^*, Sandra Rayego^*, Raquel Rodrigues-Díez^*, Javier Sánchez Rodriguez^*, Raúl Rodrigues-Díez^*, Juan Rodríguez-Vita^*, Gisselle Carvajal, Luiz Stark Aroeira, Rafael Selgas, Sergio A. Mezzano, Alberto Ortiz, Jesús Egido^|| and Marta Ruiz-Ortega^*

^* Cellular Biology in Renal Diseases Laboratory, Universidad Autónoma Madrid, Madrid, Spain; Division of Nephrology, School of Medicine, Universidad Austral, Valdivia, Chile; Servicio de Nefrología, Hospital Universitario La Paz, Madrid, Spain; Dialysis Unit, Fundación Jiménez Díaz, Madrid, Spain; and ^|| Renal Research Laboratory, Fundación Jiménez Díaz, Universidad Autónoma Madrid, Madrid, Spain

Correspondence: Marta Ruiz-Ortega, Cellular Biology in Renal Diseases Laboratory, Fundación Jiménez Díaz, Avda. Reyes Católicos, 2, 28040 Madrid, Spain. Phone: 34-91-5504821; Fax: 34-91-5442636; E-mail: mruizo{at}fjd.es

Received for publication September 22, 2008. Accepted for publication February 26, 2009.

Connective tissue growth factor (CTGF) is an important profibrotic factor in kidney diseases. Blockade of endogenous CTGF ameliorates experimental renal damage and inhibits synthesis of extracellular matrix in cultured renal cells. CTGF regulates several cellular responses, including adhesion, migration, proliferation, and synthesis of proinflammatory factors. Here, we investigated whether CTGF participates in the inflammatory process in the kidney by evaluating the nuclear factor-kappa B (NF-B) pathway, a key signaling system that controls inflammation and immune responses. Systemic administration of CTGF to mice for 24 h induced marked infiltration of inflammatory cells in the renal interstitium (T lymphocytes and monocytes/macrophages) and led to elevated renal NF-B activity. Administration of CTGF increased renal expression of chemokines (MCP-1 and RANTES) and cytokines (INF-, IL-6, and IL-4) that recruit immune cells and promote inflammation. Treatment with a NF-B inhibitor, parthenolide, inhibited CTGF-induced renal inflammatory responses, including the up-regulation of chemokines and cytokines. In cultured murine tubuloepithelial cells, CTGF rapidly activated the NF-B pathway and the cascade of mitogen-activated protein kinases, demonstrating crosstalk between these signaling pathways. CTGF, via mitogen-activated protein kinase and NF-B activation, increased proinflammatory gene expression. These data show that in addition to its profibrotic properties, CTGF contributes to the recruitment of inflammatory cells in the kidney by activating the NF-B pathway.

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673