Connective tissue growth factor is a new ligand of epidermal growth factor receptor
Entity
UAM. Departamento de MedicinaPublisher
Oxford University PressDate
2013-08-08Citation
10.1093/jmcb/mjt030
Journal of Molecular Cell Biology 5.5 (2013): 323-335
ISSN
1759-4685 (online); 1674-2788 (print)DOI
10.1093/jmcb/mjt030Funded by
This work was supported by grants from the Instituto de Salud Carlos III (ISCIII) (REDINREN RD06/0016; RD12/0021, PI081564, PI11/01854, PI12/02587, PI12/00204, and PI10/00072), Comunidad de Madrid (S2010/BMD-2321, S2010/BMD-2378), Sociedad Española de Nefrología, DIALOK Eurpean project LSHB-CT-2007-036644, and Fundacion Lilly and Research Institute Queen Sophia (FRIAT). ISCIII fellowships to R.R.D., C.L., and M.A. and programa de intensificacion (ISCIII/Lain Entralgo) to A.O.Project
Gobierno de España. RD06/0016; Gobierno de España. RD12/0021; Gobierno de España. PI081564; Gobierno de España. PI11/01854; Gobierno de España. PI12/02587; Gobierno de España. PI12/00204; Gobierno de España. PI10/00072; Comunidad de Madrid. S2010/BMD-2321; Comunidad de Madrid. S2010/BMD-2378Editor's Version
https://doi.org/10.1093/jmcb/mjt030Subjects
CCN2; receptors; EGFR; TrkA; renal; inflammation; MedicinaRights
© The Author (2013). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reservedAbstract
Chronic kidney disease is reaching epidemic proportions worldwide and there is no effective treatment. Connective tissue growth factor
(CCN2) has been suggested as a risk biomarker and a potential therapeutic target for renal diseases, but its specific receptor has not
been identified. Epidermal growth factor receptor (EGFR) participates in kidney damage, but whether CCN2 activates the EGFR pathway
is unknown. Here, we show that CCN2 is a novel EGFR ligand. CCN2 binding to EGFR extracellular domain was demonstrated by surface
plasmon resonance. CCN2 contains four distinct structural modules. The carboxyl-terminal module (CCN2(IV)) showed a clear interaction with soluble EGFR, suggesting that EGFR-binding site is located in this module. Injection of CCN2(IV) in mice increased EGFR
phosphorylation in the kidney, mainly in tubular epithelial cells. EGFR kinase inhibition decreased CCN2(IV)-induced renal changes
(ERK activation and inflammation). Studies in cultured tubular epithelial cells showed that CCN2(IV) binds to EGFR leading to ERK activation and proinflammatory factors overexpression. CCN2 interacts with the neurotrophin receptor TrkA, and EGFR/TrkA receptor crosstalk was found in response to CCN2(IV) stimulation. Moreover, endogenous CCN2 blockade inhibited TGF-b-induced EGFR activation. These findings indicate that CCN2 is a novel EGFR ligand that contributes to renal damage through EGFR signalling
Files in this item
Google Scholar:Rayego Mateos, Sandra
-
Rodrigues Díez, Raquel
-
Morgado Pascual, Jose Luis
-
Rodrigues-Diez, Raul R.
-
Mas, Sebastian
-
Lavoz, Carolina
-
Alique, Matilde
-
Pato, Janos
-
Keri, Gyorgy
-
Ortiz Arduán, Alberto
-
Ruiz Ortega, Marta
This item appears in the following Collection(s)
Related items
Showing items related by title, author, creator and subject.