2024-03-29T12:46:12Zhttps://gredos.usal.es/oai/requestoai:gredos.usal.es:10366/1407592023-02-01T11:33:58Zcom_10366_133043com_10366_4576com_10366_3823com_10366_3992com_10366_3947com_10366_3946col_10366_135272col_10366_3993
Impaired erythropoietin synthesis in chronic kidney disease is caused by alterations in extracellular matrix composition
Olmos, Gemma
Muñoz Félix, José Manuel
Mora, Inés
Müller, Anton Gerhard
Ruiz-Torres, Maria Piedad
López-Novoa, José M.
Rodríguez-Puyol, Diego
Fisiología
Anaemia
Fibrosis
Erythropoietin
Chronic kidney disease
Hypoxia-inducible factor
[EN] Renal fibrosis and anaemia are two of the most relevant events in chronic kidney disease. Fibrosis is characterized by the accumulation of extracellular
matrix proteins in the glomeruli and tubular interstitium. Anaemia is the consequence of a decrease in erythropoietin production in fibrotic
kidneys. This work analyses the possibility that the accumulation of abnormal collagens in kidney interstitium could be one of the
mechanisms responsible for erythropoietin decreased synthesis. In renal interstitial fibroblast grown on collagen I, erythropoietin mRNA
expression and HIF-2a protein decreased, whereas focal adhesion kinase protein (FAK) phosphorylation and proteasome activity increased,
compared to cells grown on collagen IV. Proteasome inhibition or FAK inactivation in cells plated on collagen I restored erythropoietin and HIF-
2a expression. FAK inhibition also decreased the collagen I-dependent proteasome activation. In a model of tubulointerstitial fibrosis induced
by unilateral ureteral obstruction in mice, increased collagen I protein content and an almost complete disappearance of erythropoietin mRNA
expression were observed in the ureteral ligated kidney with respect to the contralateral control. Interestingly, erythropoietin synthesis was
recovered in obstructed mice treated with proteasome inhibitor. These data suggest that reduced kidney erythropoietin synthesis could be
caused by the accumulation of abnormal extracellular matrix proteins.
2020-02-03T11:40:36Z
2020-02-03T11:40:36Z
2020-02-03T11:40:36Z
2018
info:eu-repo/semantics/article
Olmos, G., Muñoz‐Félix, J. M., Mora, I., Müller, A. G., Ruiz‐Torres, M. P., López‐Novoa, J. M., & Rodríguez‐Puyol, D. (2018). Impaired erythropoietin synthesis in chronic kidney disease is caused by alterations in extracellular matrix composition. Journal of cellular and molecular medicine, 22(1), 302-314.
1582-1838
http://hdl.handle.net/10366/140759
10.1111/jcmm.13319
eng
https://doi.org/10.1111/jcmm.13319
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
Attribution-NonCommercial-NoDerivatives 4.0 Internacional