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| Título: | TNF-related weak inducer of apoptosis (TWEAK) promotes kidney fibrosis and Ras-dependent proliferation of cultured renal fibroblast |
Autor: | Ucero, Alvaro C.; Santamaria, Beatriz CSIC ORCID; López-Novoa, José M.; Ruiz-Ortega, Marta | Palabras clave: | NFκB Proliferation Ras TWEAK Fn14 Kidney fibrosis |
Fecha de publicación: | 2013 | Editor: | Elsevier | Citación: | BBA - Molecular Basis of Disease 1832(10): 1744-1755 (2013) | Resumen: | Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) regulates apoptosis, proliferation and inflammation in renal epithelial cells and plays a role in acute kidney injury. However, there is little information on the chronic effects of TWEAK. We hypothesized that TWEAK may influence renal fibrosis and regulate kidney fibroblast biology, in part, through Ras pathway.We studied a chronic model of experimental unilateral ureteral obstruction in wild type and TWEAK deficient mice, and a murine model of systemic TWEAK overexpression. TWEAK actions were also explored in cultured renal and embryonic fibroblasts.TWEAK and TWEAK receptor expression was increased in the obstructed kidneys. The absence of TWEAK decreased early kidney tubular damage, inflammatory infiltrates and myofibroblast number. TWEAK deficient mice had decreased renal fibrosis 21. days after obstruction, as assessed by extracellular matrix staining. In mice without prior underlying kidney disease, systemic overexpression of TWEAK induced kidney inflammation and fibrosis. In cultured fibroblasts, TWEAK induced proliferation through activation of the Ras/ERK pathway. TWEAK also activated nuclear factor κB (NFκB)-dependent inflammatory chemokine production in murine renal fibroblasts.In conclusion, lack of TWEAK reduces renal fibrosis in a model of persistent kidney insult and overexpression of TWEAK led to renal fibrosis. TWEAK actions on renal fibroblasts may contribute to the in vivo observations, as TWEAK promotes inflammatory activity and proliferation in fibroblast cultures. © 2013 Elsevier B.V. | Descripción: | et al. | Versión del editor: | http://dx.doi.org/10.1016/j.bbadis.2013.05.032 | URI: | http://hdl.handle.net/10261/97317 | DOI: | 10.1016/j.bbadis.2013.05.032 | Identificadores: | doi: 10.1016/j.bbadis.2013.05.032 issn: 0925-4439 |
| Aparece en las colecciones: | (IIBM) Artículos |
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| Fichero | Descripción | Tamaño | Formato | |
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| TNF-related weak.pdf | 164,28 kB | Adobe PDF |  Visualizar/Abrir | |
| Supplementary Material and Methods.pdf | 65,63 kB | Adobe PDF |  Visualizar/Abrir | |
| Supplementary Figure.pdf | 49,45 kB | Adobe PDF |  Visualizar/Abrir |
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