Increased Serpina3n release into circulation during glucocorticoid‐mediated muscle atrophy
Abstract Background Glucocorticoids (GC) play a major role in muscle atrophy. As skeletal muscle is a secretory organ, characterization of the muscle secretome elicited by muscle atrophy should allow to better understand the cellular mechanisms and to identify circulating biomarkers of this conditio...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2018-10-01
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| Series: | Journal of Cachexia, Sarcopenia and Muscle |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jcsm.12315 |
| _version_ | 1797204384876068864 |
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| author | Marine Gueugneau Donatienne d'Hose Caroline Barbé Marie deBarsy Pascale Lause Dominique Maiter Laure B. Bindels Nathalie M. Delzenne Laurent Schaeffer Yann‐Gaël Gangloff Christophe Chambon Cécile Coudy‐Gandilhon Daniel Béchet Jean‐Paul Thissen |
| author_facet | Marine Gueugneau Donatienne d'Hose Caroline Barbé Marie deBarsy Pascale Lause Dominique Maiter Laure B. Bindels Nathalie M. Delzenne Laurent Schaeffer Yann‐Gaël Gangloff Christophe Chambon Cécile Coudy‐Gandilhon Daniel Béchet Jean‐Paul Thissen |
| author_sort | Marine Gueugneau |
| collection | DOAJ |
| description | Abstract Background Glucocorticoids (GC) play a major role in muscle atrophy. As skeletal muscle is a secretory organ, characterization of the muscle secretome elicited by muscle atrophy should allow to better understand the cellular mechanisms and to identify circulating biomarkers of this condition. Our project aimed to identify the changes in the muscle secretome associated with GC‐induced muscle atrophy and susceptible to translate into circulation. Methods We have identified the GC‐induced changes in the secretome of C2C12 muscle cells by proteomic analysis, and then, we have determined how these changes translate into the circulation of mice or human subjects exposed to high concentrations of GC. Results This approach led us to identify Serpina3n as one of the most markedly secreted protein in response to GC. Our original in vitro results were confirmed in vivo by an increased expression of Serpina3n in skeletal muscle (3.9‐fold; P < 0.01) and in the serum (two‐fold; P < 0.01) of mice treated with GC. We also observed increased levels of the human orthologue Serpina3 in the serum of Cushing's syndrome patients compared with healthy controls matched for age and sex (n = 9/group, 2.5‐fold; P < 0.01). An increase of Serpina3n was also demonstrated in muscle atrophy models mediated by GC such as cancer cachexia (four‐fold; P < 0.01), sepsis (12.5‐fold; P < 0.001), or diabetes (two‐fold; P < 0.01). In contrast, levels of Serpina3n both in skeletal muscle and in the circulation were reduced in several models of muscle hypertrophy induced by myostatin inhibition (P < 0.01). Furthermore, a cluster of data suggests that the regulation of muscle Serpina3n involves mTOR, an essential determinant of the muscle cell size. Conclusions Taken together, these data suggest that Serpina3n may represent a circulating biomarker of muscle atrophy associated to GC and, broadly, a reflection of dynamic changes in muscle mass. |
| first_indexed | 2024-04-24T08:34:23Z |
| format | Article |
| id | doaj.art-4a3965bb414142d984364415ff73edb7 |
| institution | Directory Open Access Journal |
| issn | 2190-5991 2190-6009 |
| language | English |
| last_indexed | 2024-04-24T08:34:23Z |
| publishDate | 2018-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Cachexia, Sarcopenia and Muscle |
| spelling | doaj.art-4a3965bb414142d984364415ff73edb72024-04-16T17:50:22ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092018-10-019592994610.1002/jcsm.12315Increased Serpina3n release into circulation during glucocorticoid‐mediated muscle atrophyMarine Gueugneau0Donatienne d'Hose1Caroline Barbé2Marie deBarsy3Pascale Lause4Dominique Maiter5Laure B. Bindels6Nathalie M. Delzenne7Laurent Schaeffer8Yann‐Gaël Gangloff9Christophe Chambon10Cécile Coudy‐Gandilhon11Daniel Béchet12Jean‐Paul Thissen13Pole of Endocrinology, Diabetes and Nutrition Institute of Experimental and Clinical Research, Université catholique de Louvain Brussels BelgiumPole of Endocrinology, Diabetes and Nutrition Institute of Experimental and Clinical Research, Université catholique de Louvain Brussels BelgiumPole of Endocrinology, Diabetes and Nutrition Institute of Experimental and Clinical Research, Université catholique de Louvain Brussels BelgiumPole of Endocrinology, Diabetes and Nutrition Institute of Experimental and Clinical Research, Université catholique de Louvain Brussels BelgiumPole of Endocrinology, Diabetes and Nutrition Institute of Experimental and Clinical Research, Université catholique de Louvain Brussels BelgiumPole of Endocrinology, Diabetes and Nutrition Institute of Experimental and Clinical Research, Université catholique de Louvain Brussels BelgiumMetabolism and Nutrition Research Group Louvain Drug Research Institute (LDRI), Université catholique de Louvain Brussels BelgiumMetabolism and Nutrition Research Group Louvain Drug Research Institute (LDRI), Université catholique de Louvain Brussels BelgiumINMG, CNRS, UMR 5310, INSERM U1217, LBMC, Ecole Normale Supérieure de Lyon Lyon FranceINMG, CNRS, UMR 5310, INSERM U1217, LBMC, Ecole Normale Supérieure de Lyon Lyon FranceINRA, Plateforme d'Exploration du Métabolisme Composante Protéomique Saint Genès Champanelle FranceINRA, UMR1019, Université Clermont Auvergne, UNH, Unité de Nutrition Humaine, CRNH Auvergne Clermont‐Ferrand FranceINRA, UMR1019, Université Clermont Auvergne, UNH, Unité de Nutrition Humaine, CRNH Auvergne Clermont‐Ferrand FrancePole of Endocrinology, Diabetes and Nutrition Institute of Experimental and Clinical Research, Université catholique de Louvain Brussels BelgiumAbstract Background Glucocorticoids (GC) play a major role in muscle atrophy. As skeletal muscle is a secretory organ, characterization of the muscle secretome elicited by muscle atrophy should allow to better understand the cellular mechanisms and to identify circulating biomarkers of this condition. Our project aimed to identify the changes in the muscle secretome associated with GC‐induced muscle atrophy and susceptible to translate into circulation. Methods We have identified the GC‐induced changes in the secretome of C2C12 muscle cells by proteomic analysis, and then, we have determined how these changes translate into the circulation of mice or human subjects exposed to high concentrations of GC. Results This approach led us to identify Serpina3n as one of the most markedly secreted protein in response to GC. Our original in vitro results were confirmed in vivo by an increased expression of Serpina3n in skeletal muscle (3.9‐fold; P < 0.01) and in the serum (two‐fold; P < 0.01) of mice treated with GC. We also observed increased levels of the human orthologue Serpina3 in the serum of Cushing's syndrome patients compared with healthy controls matched for age and sex (n = 9/group, 2.5‐fold; P < 0.01). An increase of Serpina3n was also demonstrated in muscle atrophy models mediated by GC such as cancer cachexia (four‐fold; P < 0.01), sepsis (12.5‐fold; P < 0.001), or diabetes (two‐fold; P < 0.01). In contrast, levels of Serpina3n both in skeletal muscle and in the circulation were reduced in several models of muscle hypertrophy induced by myostatin inhibition (P < 0.01). Furthermore, a cluster of data suggests that the regulation of muscle Serpina3n involves mTOR, an essential determinant of the muscle cell size. Conclusions Taken together, these data suggest that Serpina3n may represent a circulating biomarker of muscle atrophy associated to GC and, broadly, a reflection of dynamic changes in muscle mass.https://doi.org/10.1002/jcsm.12315Serpina3nGlucocorticoidsMuscle atrophyBiomarker |
| spellingShingle | Marine Gueugneau Donatienne d'Hose Caroline Barbé Marie deBarsy Pascale Lause Dominique Maiter Laure B. Bindels Nathalie M. Delzenne Laurent Schaeffer Yann‐Gaël Gangloff Christophe Chambon Cécile Coudy‐Gandilhon Daniel Béchet Jean‐Paul Thissen Increased Serpina3n release into circulation during glucocorticoid‐mediated muscle atrophy Journal of Cachexia, Sarcopenia and Muscle Serpina3n Glucocorticoids Muscle atrophy Biomarker |
| title | Increased Serpina3n release into circulation during glucocorticoid‐mediated muscle atrophy |
| title_full | Increased Serpina3n release into circulation during glucocorticoid‐mediated muscle atrophy |
| title_fullStr | Increased Serpina3n release into circulation during glucocorticoid‐mediated muscle atrophy |
| title_full_unstemmed | Increased Serpina3n release into circulation during glucocorticoid‐mediated muscle atrophy |
| title_short | Increased Serpina3n release into circulation during glucocorticoid‐mediated muscle atrophy |
| title_sort | increased serpina3n release into circulation during glucocorticoid mediated muscle atrophy |
| topic | Serpina3n Glucocorticoids Muscle atrophy Biomarker |
| url | https://doi.org/10.1002/jcsm.12315 |
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