Balance between apoptosis or survival induced by changes in extracellular-matrix composition in human mesangial cells: a key role for ILK-NFκB pathway
Entity
UAM. Departamento de BioquímicaPublisher
SpringerDate
2012-10-10Citation
10.1007/s10495-012-0769-3
Apoptosis 17 (2012): 1261-1274
ISSN
1573-675X (online); 1360-8185 (print)DOI
10.1007/s10495-012-0769-3Funded by
This study was supported by Grant ISCIIIRETIC (REDinREN/RD06/0016/0002), by Grant Fundación Mutua Madrileña (FMM2011-001) to LC, by Grant Ministerio de Educación (SAF2010-16198) to MRP and by Grant Fondo de Investigaciones Sanitarias (FISSPI11/01630) to DRPProject
Gobierno de España. SAF2010-16198; Gobierno de España. PI11/01630Editor's Version
https://doi.org/10.1007/s10495-012-0769-3Subjects
Apoptosis; NFjB; ILK; Cell–matrixinteractions; Collagen; renal fibrosis; MedicinaRights
© Springer Science+Business Media New York 2012Abstract
Renal fibrosis is the final outcome of many clinical conditions that lead to chronic renal failure, characterized by a progressive substitution of cellular elements by extracellular-matrix proteins, in particular collagen type I. The aim of this study was to identify the mechanisms responsible for human mesangial cell survival, conditioned by changes in extracellular-matrix composition. Our results indicate that collagen I induces apoptosis in cells but only after inactivation of the pro-survival factor NFκB by either the super-repressor IκBα or the PDTC inhibitor. Collagen I activates a death pathway, through ILK/GSK-3β-dependent Bim expression. Moreover, collagen I significantly increases NFκB-dependent transcription, IκBα degradation and p65/NFκB translocation to the nucleus; it activates β1 integrin and this is accompanied by increased activity of ILK which leads to AKT activation. Knockdown of ILK or AKT with small interfering RNA suppresses the increase in NFκB activity. NFκB mediates cell survival through the antiapoptotic protein Bcl-xL. Our data suggest that human mesangial cells exposed to abnormal collagen I are protected against apoptosis by a complex mechanism involving integrin β1/ILK/AKT-dependent NFκB activation with consequent Bcl-xL overexpression, that opposes a simultaneously activated ILK/GSK-3β-dependent Bim expression and this dual mechanism may play a role in the progression of glomerular dysfunction
Files in this item
Google Scholar:Nogal, María del
-
Luengo, Alicia
-
Olmos, Gemma
-
Lasa Benito, Marina Paloma
-
Rodríguez Puyol, Diego
-
Rodríguez Puyol, Manuel
-
Calleros, Laura
This item appears in the following Collection(s)
Related items
Showing items related by title, author, creator and subject.
-
Population-based multicase-control study in common tumors in Spain (MCC-Spain): Rationale and study design
Castaño-Vinyals, Gemma; Aragonés, Nuria; Pérez-Gómez, Beatriz; Martín, Vicente; Llorca, Javier; Moreno, Víctor; Altzibar, Jone M.; Ardanaz, Eva; De Sanjosé, Sílvia; Jiménez-Moleón, José J.; Tardón, Adonina; Alguacil, Juan; Peiró, Rosana; Marcos-Gragera, Rafael; Navarro, Carmen; Pollán Santamaría, Marina Anunciación; Kogevinas, Manolis; Alonso, Maria Teresa; Amiano, Pilar; Arias, Cristina; Azpiri, Mikel; Benavente, Yolanda; Boldo, Elena; Bueno, Aurora; Bustamante, Mariona; Caballero, Francisco Javier; Campo, Elías; Cantón, Rafael; Capelo, Rocío; Carmona, Carme; Casabonne, Delphine; Chirlaque, María Dolores; Cirac, Judith; Clofent, Juan; Colado, Enrique; Costas, Laura; Crous, Marta; Campo, Rosa del; Díaz Santos, Marian; Dierssen-Sotos, Trinidad; Ederra, María; Espinosa, Ana; Fernández Cabrera, Marieta; Fernández Somoano, Ana; Fernández Villa, Tania; García García-Esquinas, Esther; García Martín, Paloma; Gómez-Acebo, Inés; Puga, Cristina González; Gràcia, Esther; Eslava, Marcela Guevara; Guinó, Elisabet; Huerta, José María; Lope, Virginia; López-Abente, Gonzalo; López-Otín, Carlos; Martínez Argüelles, Begoña; Merino Salas, Sergio; Mirón Pozo, Benito; Molina dee La Torre, Antonio José; Moreno, Eduardo; Moreno Iribas, Concepción; Olea, Nicolás; Gelis, Gemma Osca; Paré, Laia; Porta, Miquel; Puig, Montse; Rivad del Fresno, Manuel; Robles, Claudia; Rodríguez Suarez, Marta María; Romero, Beatriz; Sáez Castillo, Ana Isabel; Sala Serra, Maria
2015-01-01