Altered expression of proteins involved in metabolism in LGMDR1 muscle is lost in cell culture conditions

Vista sencilla de ítem
dc.contributor.authorRico, Anabel
dc.contributor.authorValls Rodríguez, Andrea
dc.contributor.authorGuembelzu, Garazi
dc.contributor.authorAzpitarte Lizaso, Margarita
dc.contributor.authorAiastui Pujana, Ana
dc.contributor.authorZufiría García, Mónica
dc.contributor.authorJaka, Oihane
dc.contributor.authorLópez de Munain Arregui, Adolfo
dc.contributor.authorSáenz, Amets
dc.date.accessioned2025-07-28T11:10:50Z
dc.date.available2025-07-28T11:10:50Z
dc.date.issued2023-10-10
dc.date.updated2025-07-28T11:10:50Z
dc.description.abstractBackground: Limb-girdle muscular dystrophy R1 calpain 3-related (LGMDR1) is an autosomal recessive muscular dystrophy due to mutations in the CAPN3 gene. While the pathophysiology of this disease has not been clearly established yet, Wnt and mTOR signaling pathways impairment in LGMDR1 muscles has been reported. Results: A reduction in Akt phosphorylation ratio and upregulated expression of proteins implicated in glycolysis (HK-II) and in fructose and lactate transport (GLUT5 and MCT1) in LGMDR1 muscle was observed. In vitro analysis to establish mitochondrial and glycolytic functions of primary cultures were performed, however, no differences between control and patients were observed. Additionally, gene expression analysis showed a lack of correlation between primary myoblasts/myotubes and LGMDR1 muscle while skin fibroblasts and CD56− cells showed a slightly better correlation with muscle. FRZB gene was upregulated in all the analyzed cell types (except in myoblasts). Conclusions: Proteins implicated in metabolism are deregulated in LGMDR1 patients’ muscle. Obtained results evidence the limited usefulness of primary myoblasts/myotubes for LGMDR1 gene expression and metabolic studies. However, since FRZB is the only gene that showed upregulation in all the analyzed cell types it is suggested its role as a key regulator of the pathophysiology of the LGMDR1 muscle fiber. The Wnt signaling pathway inactivation, secondary to FRZB upregulation, and GLUT5 overexpression may participate in the impaired adipogenesis in LGMD1R patients.en
dc.description.sponsorshipThis study has been funded by Instituto de Salud Carlos III (ISCIII) through the projects PI16/01325, PI17/01841, PI21/00047 and DTS19/00061 and cofunded by the European Union. It was, in part, supported by the Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED: CB06/05/1126 to A.R., G.G., A.V., O.J., A.L.d.M. and A.S.), GENE (Association of Neuromuscular diseases of Gipuzkoa) and Fundación La Caixa. A.R. was supported by the predoctoral fellowship given by the department of Education, Universities and Research of the Basque Government (PRE-2016-1-0382en
dc.identifier.citationRico, A., Valls, A., Guembelzu, G., Azpitarte, M., Aiastui, A., Zufiria, M., Jaka, O., López de Munain, A., & Sáenz, A. (2023). Altered expression of proteins involved in metabolism in LGMDR1 muscle is lost in cell culture conditions. Orphanet Journal of Rare Diseases, 18(1). https://doi.org/10.1186/S13023-023-02873-5
dc.identifier.doi10.1186/S13023-023-02873-5
dc.identifier.eissn1750-1172
dc.identifier.urihttps://hdl.handle.net/20.500.14454/3289
dc.language.isoeng
dc.publisherBioMed Central Ltd
dc.rights© The Author(s) 2023
dc.subject.otherCalpain 3
dc.subject.otherCD56−
dc.subject.otherCell culture
dc.subject.otherFRZB
dc.subject.otherGLUT5
dc.subject.otherHKII
dc.subject.otherLGMDR1
dc.subject.otherMCT1
dc.subject.otherMetabolism
dc.subject.otherMyoblast
dc.subject.otherMyotubes
dc.titleAltered expression of proteins involved in metabolism in LGMDR1 muscle is lost in cell culture conditionsen
dc.typejournal article
dcterms.accessRightsopen access
oaire.citation.issue1
oaire.citation.titleOrphanet Journal of Rare Diseases
oaire.citation.volume18
oaire.licenseConditionhttps://creativecommons.org/licenses/by/4.0/
oaire.versionVoR
Archivos
Bloque original
Mostrando 1 - 1 de 1
Miniatura
Nombre:
rico_altered_2023.pdf
Tamaño:
2.11 MB
Formato:
Adobe Portable Document Format
Descargar
Colecciones
Artículos