CCN2 Binds to Tubular Epithelial Cells in the Kidney
EntityUAM. Departamento de Medicina
10.3390/biom12020252Biomolecules 12.2 (2022): 252
Funded byThis research was funded by grants from the Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union (PI17/00119, PI20/00140, and DTS20/00083), Sara Borrell’ program from Instituto de Salud Carlos III (ISCIII) (grant number CD20/00042 to R.R.R-D), Red de Investigación Renal REDINREN: RD16/0009 and RICORS program to RICORS2040 (RD21/0005) to M.R-O. Sociedad Española de Nefrología, “NOVELREN-CM: Enfermedad renal crónica: nuevas Estrategias para la prevención, Diagnóstico y tratamiento” (B2017/BMD-3751 to M.R.-O.), “Convocatoria Dinamización Europa Investigación 2019” MINECO (EIN2019-103294 to M.R.-O. and S.R.-M.), Juan de la Cierva formación grant: FJC2019-042028-I to J.L.M.-P., and Juan de la Cierva incorporación grant: IJC2018-035187-I to S.R.-M
ProjectGobierno de España. PI17/00119; Gobierno de España. PI20/00140; Gobierno de España. EIN2019-103294
SubjectsCCN2; CTGF; EGFR; Kidney damage; Medicina
Rights© 2022 by the authors
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
Cellular communication network-2 (CCN2), also called connective tissue growth factor (CTGF), is considered a fibrotic biomarker and has been suggested as a potential therapeutic target for kidney pathologies. CCN2 is a matricellular protein with four distinct structural modules that can exert a dual function as a matricellular protein and as a growth factor. Previous experiments using surface plasmon resonance and cultured renal cells have demonstrated that the C-terminal module of CCN2 (CCN2(IV)) interacts with the epidermal growth factor receptor (EGFR). Moreover, CCN2(IV) activates proinflammatory and profibrotic responses in the mouse kidney. The aim of this paper was to locate the in vivo cellular CCN2/EGFR binding sites in the kidney. To this aim, the C-terminal module CCN2(IV) was labeled with a fluorophore (Cy5), and two different administration routes were employed. Both intraperitoneal and direct intra-renal injection of Cy5-CCN2(IV) in mice demonstrated that CCN2(IV) preferentially binds to the tubular epithelial cells, while no signal was detected in glomeruli. Moreover, co-localization of Cy5-CCN2(IV) binding and activated EGFR was found in tubules. In cultured tubular epithelial cells, live-cell confocal microscopy experiments showed that EGFR gene silencing blocked Cy5-CCN2(IV) binding to tubuloepithelial cells. These data clearly show the existence of CCN2/EGFR binding sites in the kidney, mainly in tubular epithelial cells. In conclusion, these studies show that circulating CCN2(IV) can directly bind and activate tubular cells, supporting the role of CCN2 as a growth factor involved in kidney damage progression
Google Scholar:Rayego-Mateos, Sandra - Morgado-Pascual, José Luis - Lavoz, Carolina - Rodrigues-Diez, Raul R. - Márquez-Expósito, Laura - Tejera-Muñoz, Antonio - Tejedor Santamaria, Lucía - Rubio-Soto, Irene - Marchant, Vanessa - Ruiz Ortega, Marta
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