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Secreted protein acidic and rich in cysteine internalization and its age-related alterations in skeletal muscle progenitor cells

Aging causes phenotypic changes in skeletal muscle progenitor cells (Skm-PCs), such as reduced myogenesis and increased adipogenesis due to alterations in their environment or niche. Secreted protein acidic and rich in cysteine (SPARC), which is secreted into the niche of Skm-PCs, inhibits adipogene...

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Autores principales: Nakamura, Katsuyuki, Yamanouchi, Keitaro, Nishihara, Masugi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326877/
https://www.ncbi.nlm.nih.gov/pubmed/24245505
http://dx.doi.org/10.1111/acel.12168
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author Nakamura, Katsuyuki
Yamanouchi, Keitaro
Nishihara, Masugi
author_facet Nakamura, Katsuyuki
Yamanouchi, Keitaro
Nishihara, Masugi
author_sort Nakamura, Katsuyuki
collection PubMed
description Aging causes phenotypic changes in skeletal muscle progenitor cells (Skm-PCs), such as reduced myogenesis and increased adipogenesis due to alterations in their environment or niche. Secreted protein acidic and rich in cysteine (SPARC), which is secreted into the niche of Skm-PCs, inhibits adipogenesis and promotes myogenesis. We have previously reported that Skm-PC responsiveness to SPARC declines with age, although the mechanism underlying this decline is unknown. In this study, we found that SPARC is internalized by Skm-PCs and that this uptake increases with age. Internalization is dependent on integrin-α5, a cell surface SPARC-binding molecule, and clathrin-mediated endocytosis. We also demonstrated that internalized SPARC is transported to Rab7-positive endosomes. Skm-PCs from old rats exhibited increased clathrin expression and decreased Rab7 expression exclusively in MyoD-negative cells. In loss-of-function analyses, clathrin knockdown increased the anti-adipogenic effect of SPARC, whereas Rab7 knockdown reduced it, indicating that alterations in SPARC internalization may mediate the age-related decline in its anti-adipogenic effect. These results provide insights into age-related SPARC resistance in Skm-PCs, which may lead to sarcopenia.
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spelling pubmed-43268772015-02-19 Secreted protein acidic and rich in cysteine internalization and its age-related alterations in skeletal muscle progenitor cells Nakamura, Katsuyuki Yamanouchi, Keitaro Nishihara, Masugi Aging Cell Original Articles Aging causes phenotypic changes in skeletal muscle progenitor cells (Skm-PCs), such as reduced myogenesis and increased adipogenesis due to alterations in their environment or niche. Secreted protein acidic and rich in cysteine (SPARC), which is secreted into the niche of Skm-PCs, inhibits adipogenesis and promotes myogenesis. We have previously reported that Skm-PC responsiveness to SPARC declines with age, although the mechanism underlying this decline is unknown. In this study, we found that SPARC is internalized by Skm-PCs and that this uptake increases with age. Internalization is dependent on integrin-α5, a cell surface SPARC-binding molecule, and clathrin-mediated endocytosis. We also demonstrated that internalized SPARC is transported to Rab7-positive endosomes. Skm-PCs from old rats exhibited increased clathrin expression and decreased Rab7 expression exclusively in MyoD-negative cells. In loss-of-function analyses, clathrin knockdown increased the anti-adipogenic effect of SPARC, whereas Rab7 knockdown reduced it, indicating that alterations in SPARC internalization may mediate the age-related decline in its anti-adipogenic effect. These results provide insights into age-related SPARC resistance in Skm-PCs, which may lead to sarcopenia. BlackWell Publishing Ltd 2014-02 2013-11-19 /pmc/articles/PMC4326877/ /pubmed/24245505 http://dx.doi.org/10.1111/acel.12168 Text en © 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Nakamura, Katsuyuki
Yamanouchi, Keitaro
Nishihara, Masugi
Secreted protein acidic and rich in cysteine internalization and its age-related alterations in skeletal muscle progenitor cells
title Secreted protein acidic and rich in cysteine internalization and its age-related alterations in skeletal muscle progenitor cells
title_full Secreted protein acidic and rich in cysteine internalization and its age-related alterations in skeletal muscle progenitor cells
title_fullStr Secreted protein acidic and rich in cysteine internalization and its age-related alterations in skeletal muscle progenitor cells
title_full_unstemmed Secreted protein acidic and rich in cysteine internalization and its age-related alterations in skeletal muscle progenitor cells
title_short Secreted protein acidic and rich in cysteine internalization and its age-related alterations in skeletal muscle progenitor cells
title_sort secreted protein acidic and rich in cysteine internalization and its age-related alterations in skeletal muscle progenitor cells
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326877/
https://www.ncbi.nlm.nih.gov/pubmed/24245505
http://dx.doi.org/10.1111/acel.12168
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