Uraemic toxins impair skeletal muscle regeneration by inhibiting myoblast proliferation, reducing myogenic differentiation, and promoting muscular fibrosis

Abstract Uraemic toxins increase in serum parallel to a decline in the glomerular filtration rate and the development of sarcopenia in patients with chronic kidney disease (CKD). This study analyses the role of uraemic toxins in sarcopenia at different stages of CKD, evaluating changes in the muscul...

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Autores principales:	Elena Alcalde-Estévez, Patricia Sosa, Ana Asenjo-Bueno, Patricia Plaza, Gemma Olmos, Manuel Naves-Díaz, Diego Rodríguez-Puyol, Susana López-Ongil, María P. Ruiz-Torres
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4b37d63023314b8291db168f8e4ec209
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spelling	oai:doaj.org-article:4b37d63023314b8291db168f8e4ec2092021-12-02T15:22:59ZUraemic toxins impair skeletal muscle regeneration by inhibiting myoblast proliferation, reducing myogenic differentiation, and promoting muscular fibrosis10.1038/s41598-020-79186-12045-2322https://doaj.org/article/4b37d63023314b8291db168f8e4ec2092021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79186-1https://doaj.org/toc/2045-2322Abstract Uraemic toxins increase in serum parallel to a decline in the glomerular filtration rate and the development of sarcopenia in patients with chronic kidney disease (CKD). This study analyses the role of uraemic toxins in sarcopenia at different stages of CKD, evaluating changes in the muscular regeneration process. Cultured C2C12 cells were incubated with a combination of indoxyl sulphate and p-cresol at high doses (100 µg/mL) or low doses (25 µg/mL and 10 µg/mL) resembling late or early CKD stages, respectively. Cell proliferation (analysed by scratch assays and flow cytometry) was inhibited only by high doses of uraemic toxins, which inactivated the cdc2-cyclin B complex, inhibiting mitosis and inducing apoptosis (analysed by annexin V staining). By contrast, low doses of uraemic toxins did not affect proliferation, but reduced myogenic differentiation, primed with 2% horse serum, by inhibiting myogenin expression and promoting fibro-adipogenic differentiation. Finally, to assess the in vivo relevance of these results, studies were performed in gastrocnemii from uraemic rats, which showed higher collagen expression and lower myosin heavy chain expression than those from healthy rats. In conclusion, uraemic toxins impair the skeletal muscular regeneration process, even at low concentrations, suggesting that sarcopenia can progress from the early stages of CKD.Elena Alcalde-EstévezPatricia SosaAna Asenjo-BuenoPatricia PlazaGemma OlmosManuel Naves-DíazDiego Rodríguez-PuyolSusana López-OngilMaría P. Ruiz-TorresNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elena Alcalde-Estévez Patricia Sosa Ana Asenjo-Bueno Patricia Plaza Gemma Olmos Manuel Naves-Díaz Diego Rodríguez-Puyol Susana López-Ongil María P. Ruiz-Torres Uraemic toxins impair skeletal muscle regeneration by inhibiting myoblast proliferation, reducing myogenic differentiation, and promoting muscular fibrosis
description	Abstract Uraemic toxins increase in serum parallel to a decline in the glomerular filtration rate and the development of sarcopenia in patients with chronic kidney disease (CKD). This study analyses the role of uraemic toxins in sarcopenia at different stages of CKD, evaluating changes in the muscular regeneration process. Cultured C2C12 cells were incubated with a combination of indoxyl sulphate and p-cresol at high doses (100 µg/mL) or low doses (25 µg/mL and 10 µg/mL) resembling late or early CKD stages, respectively. Cell proliferation (analysed by scratch assays and flow cytometry) was inhibited only by high doses of uraemic toxins, which inactivated the cdc2-cyclin B complex, inhibiting mitosis and inducing apoptosis (analysed by annexin V staining). By contrast, low doses of uraemic toxins did not affect proliferation, but reduced myogenic differentiation, primed with 2% horse serum, by inhibiting myogenin expression and promoting fibro-adipogenic differentiation. Finally, to assess the in vivo relevance of these results, studies were performed in gastrocnemii from uraemic rats, which showed higher collagen expression and lower myosin heavy chain expression than those from healthy rats. In conclusion, uraemic toxins impair the skeletal muscular regeneration process, even at low concentrations, suggesting that sarcopenia can progress from the early stages of CKD.
format	article
author	Elena Alcalde-Estévez Patricia Sosa Ana Asenjo-Bueno Patricia Plaza Gemma Olmos Manuel Naves-Díaz Diego Rodríguez-Puyol Susana López-Ongil María P. Ruiz-Torres
author_facet	Elena Alcalde-Estévez Patricia Sosa Ana Asenjo-Bueno Patricia Plaza Gemma Olmos Manuel Naves-Díaz Diego Rodríguez-Puyol Susana López-Ongil María P. Ruiz-Torres
author_sort	Elena Alcalde-Estévez
title	Uraemic toxins impair skeletal muscle regeneration by inhibiting myoblast proliferation, reducing myogenic differentiation, and promoting muscular fibrosis
title_short	Uraemic toxins impair skeletal muscle regeneration by inhibiting myoblast proliferation, reducing myogenic differentiation, and promoting muscular fibrosis
title_full	Uraemic toxins impair skeletal muscle regeneration by inhibiting myoblast proliferation, reducing myogenic differentiation, and promoting muscular fibrosis
title_fullStr	Uraemic toxins impair skeletal muscle regeneration by inhibiting myoblast proliferation, reducing myogenic differentiation, and promoting muscular fibrosis
title_full_unstemmed	Uraemic toxins impair skeletal muscle regeneration by inhibiting myoblast proliferation, reducing myogenic differentiation, and promoting muscular fibrosis
title_sort	uraemic toxins impair skeletal muscle regeneration by inhibiting myoblast proliferation, reducing myogenic differentiation, and promoting muscular fibrosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4b37d63023314b8291db168f8e4ec209
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Uraemic toxins impair skeletal muscle regeneration by inhibiting myoblast proliferation, reducing myogenic differentiation, and promoting muscular fibrosis

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