Role of Calpains in Uremia-Related Functional and Structural Muscle Changes: Protective Effect of Calpastatin Overexpression
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| Publicat a: | Cells vol. 14, no. 23 (2025), p. 1846-1866 |
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| Autor principal: | |
| Altres autors: | , , , , , , , , , , |
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MDPI AG
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| Accés en línia: | Citation/Abstract Full Text + Graphics Full Text - PDF |
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| 001 | 3280947062 | ||
| 003 | UK-CbPIL | ||
| 022 | |a 2073-4409 | ||
| 024 | 7 | |a 10.3390/cells14231846 |2 doi | |
| 035 | |a 3280947062 | ||
| 045 | 2 | |b d20250101 |b d20251231 | |
| 084 | |a 231441 |2 nlm | ||
| 100 | 1 | |a Gutiérrez-Calabrés, Elena |u Physiology Unit, Department of Systems Biology, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain; sofia.campillo@uah.es (S.C.); elena.alcaldee@uah.es (E.A.-E.); sergio.garciavillori@uah.es (S.G.-V.); alba.silvestre@uah.es (A.S.-V.); mercedes.griera@uah.es (M.G.); sergio.frutos@uah.es (S.d.F.); mpiedad.ruiz@uah.es (M.P.R.-T.); laura.calleros@uah.es (L.C.) | |
| 245 | 1 | |a Role of Calpains in Uremia-Related Functional and Structural Muscle Changes: Protective Effect of Calpastatin Overexpression | |
| 260 | |b MDPI AG |c 2025 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a <sec sec-type="highlights"> What are the main findings? <list list-type="bullet"> <list-item> </list-item>Adenine-induced CKD leads to a decline in muscle strength and deterioration of muscle quality, even in the absence of significant muscle mass loss. <list-item> Uremic conditions upregulate CAPN2 expression and activity in skeletal muscle, suggesting a pathogenic role in muscle deterioration. </list-item> <list-item> Inhibition of calpain activity through CAST overexpression preserves muscle function and attenuates fibrosis, inflammation and adipogenic processes. </list-item> <list-item> The protective effects of CAPN inhibition occur independently of improvements in renal function. </list-item> What is the implication of the main finding? <list list-type="bullet"> <list-item> </list-item>CAPN2 emerges as a potential therapeutic target to prevent sarcopenia in CKD. Sarcopenia, the progressive loss of muscle mass and strength, is a common complication in patients with chronic kidney disease (CKD). This condition arises from a combination of factors including reduced physical activity, insufficient protein intake, hyperphosphatemia, chronic inflammation, and uremia itself; however, the underlying molecular mechanisms remain poorly understood. Proteolysis in skeletal muscle is primarily controlled by the ubiquitin–proteasome system, autophagy–lysosome system, and calpains (CAPNs) cysteine proteases, which degrade structural proteins and mediate cell signaling. This study aims to investigate the role of CAPNs in CKD-associated muscle deterioration. CKD was induced in mice through an adenine-rich diet for 2, 4 and 6 weeks. The involvement of CAPNs in CKD-related sarcopenia was assessed using mice that overexpressed the CAPNs endogenous inhibitor, calpastatin (CAST). Gastrocnemius muscle strength, structural integrity, and function were evaluated. Mice with CKD showed elevated CAPNs, particularly CAPN2, expression and activity in the gastrocnemius, in parallel with significant muscle deterioration, including strength loss, structural damage, and impaired muscle performance. Overexpression of CAST prevented muscle strength loss, improved muscle function and structure without affecting renal function, and reversed fibrosis, inflammation and adipogenesis expression markers. Targeting CAPN2 could be a promising therapeutic strategy to mitigate muscle damage and improve physical performance in CKD patients. | |
| 610 | 4 | |a Agilent Technologies Inc | |
| 651 | 4 | |a United States--US | |
| 651 | 4 | |a Germany | |
| 653 | |a Plasma | ||
| 653 | |a Physical activity | ||
| 653 | |a Calpastatin | ||
| 653 | |a Proteasomes | ||
| 653 | |a Autophagy | ||
| 653 | |a Animals | ||
| 653 | |a Structural proteins | ||
| 653 | |a Sarcopenia | ||
| 653 | |a Kidney diseases | ||
| 653 | |a Therapeutic targets | ||
| 653 | |a Molecular modelling | ||
| 653 | |a Proteases | ||
| 653 | |a Ubiquitin | ||
| 653 | |a Muscle strength | ||
| 653 | |a Gastrocnemius muscle | ||
| 653 | |a Apoptosis | ||
| 653 | |a Oxidative stress | ||
| 653 | |a Proteolysis | ||
| 653 | |a Inflammation | ||
| 653 | |a Adipogenesis | ||
| 653 | |a Uremia | ||
| 653 | |a Calpain | ||
| 653 | |a Musculoskeletal system | ||
| 653 | |a Skeletal muscle | ||
| 653 | |a Hyperphosphatemia | ||
| 653 | |a Renal function | ||
| 653 | |a Structure-function relationships | ||
| 653 | |a Fibrosis | ||
| 653 | |a Cell signaling | ||
| 653 | |a Creatinine | ||
| 700 | 1 | |a Campillo Sofía |u Physiology Unit, Department of Systems Biology, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain; sofia.campillo@uah.es (S.C.); elena.alcaldee@uah.es (E.A.-E.); sergio.garciavillori@uah.es (S.G.-V.); alba.silvestre@uah.es (A.S.-V.); mercedes.griera@uah.es (M.G.); sergio.frutos@uah.es (S.d.F.); mpiedad.ruiz@uah.es (M.P.R.-T.); laura.calleros@uah.es (L.C.) | |
| 700 | 1 | |a Alcalde-Estévez, Elena |u Physiology Unit, Department of Systems Biology, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain; sofia.campillo@uah.es (S.C.); elena.alcaldee@uah.es (E.A.-E.); sergio.garciavillori@uah.es (S.G.-V.); alba.silvestre@uah.es (A.S.-V.); mercedes.griera@uah.es (M.G.); sergio.frutos@uah.es (S.d.F.); mpiedad.ruiz@uah.es (M.P.R.-T.); laura.calleros@uah.es (L.C.) | |
| 700 | 1 | |a Cuevas-Delgado, Paula |u Centre for Metabolomics and Bioanalysis (CEMBIO), Chemistry and Biochemistry Department, Pharmacy Faculty, Universidad San Pablo-CEU, 28871 Boadilla del Monte, Madrid, Spain; pau.cuevas.ce@ceindo.ceu.es (P.C.-D.); cbarbas@ceu.es (C.B.) | |
| 700 | 1 | |a Barbas Coral |u Centre for Metabolomics and Bioanalysis (CEMBIO), Chemistry and Biochemistry Department, Pharmacy Faculty, Universidad San Pablo-CEU, 28871 Boadilla del Monte, Madrid, Spain; pau.cuevas.ce@ceindo.ceu.es (P.C.-D.); cbarbas@ceu.es (C.B.) | |
| 700 | 1 | |a García-Villoria, Sergio |u Physiology Unit, Department of Systems Biology, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain; sofia.campillo@uah.es (S.C.); elena.alcaldee@uah.es (E.A.-E.); sergio.garciavillori@uah.es (S.G.-V.); alba.silvestre@uah.es (A.S.-V.); mercedes.griera@uah.es (M.G.); sergio.frutos@uah.es (S.d.F.); mpiedad.ruiz@uah.es (M.P.R.-T.); laura.calleros@uah.es (L.C.) | |
| 700 | 1 | |a Silvestre-Vargas, Alba |u Physiology Unit, Department of Systems Biology, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain; sofia.campillo@uah.es (S.C.); elena.alcaldee@uah.es (E.A.-E.); sergio.garciavillori@uah.es (S.G.-V.); alba.silvestre@uah.es (A.S.-V.); mercedes.griera@uah.es (M.G.); sergio.frutos@uah.es (S.d.F.); mpiedad.ruiz@uah.es (M.P.R.-T.); laura.calleros@uah.es (L.C.) | |
| 700 | 1 | |a Griera Mercedes |u Physiology Unit, Department of Systems Biology, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain; sofia.campillo@uah.es (S.C.); elena.alcaldee@uah.es (E.A.-E.); sergio.garciavillori@uah.es (S.G.-V.); alba.silvestre@uah.es (A.S.-V.); mercedes.griera@uah.es (M.G.); sergio.frutos@uah.es (S.d.F.); mpiedad.ruiz@uah.es (M.P.R.-T.); laura.calleros@uah.es (L.C.) | |
| 700 | 1 | |a de Frutos Sergio |u Physiology Unit, Department of Systems Biology, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain; sofia.campillo@uah.es (S.C.); elena.alcaldee@uah.es (E.A.-E.); sergio.garciavillori@uah.es (S.G.-V.); alba.silvestre@uah.es (A.S.-V.); mercedes.griera@uah.es (M.G.); sergio.frutos@uah.es (S.d.F.); mpiedad.ruiz@uah.es (M.P.R.-T.); laura.calleros@uah.es (L.C.) | |
| 700 | 1 | |a Ruiz-Torres, María P |u Physiology Unit, Department of Systems Biology, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain; sofia.campillo@uah.es (S.C.); elena.alcaldee@uah.es (E.A.-E.); sergio.garciavillori@uah.es (S.G.-V.); alba.silvestre@uah.es (A.S.-V.); mercedes.griera@uah.es (M.G.); sergio.frutos@uah.es (S.d.F.); mpiedad.ruiz@uah.es (M.P.R.-T.); laura.calleros@uah.es (L.C.) | |
| 700 | 1 | |a Rodríguez-Puyol, Diego |u Fundación Renal Española, 28871 Madrid, Spain; diego.rodriguez@uah.es | |
| 700 | 1 | |a Calleros, Laura |u Physiology Unit, Department of Systems Biology, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain; sofia.campillo@uah.es (S.C.); elena.alcaldee@uah.es (E.A.-E.); sergio.garciavillori@uah.es (S.G.-V.); alba.silvestre@uah.es (A.S.-V.); mercedes.griera@uah.es (M.G.); sergio.frutos@uah.es (S.d.F.); mpiedad.ruiz@uah.es (M.P.R.-T.); laura.calleros@uah.es (L.C.) | |
| 773 | 0 | |t Cells |g vol. 14, no. 23 (2025), p. 1846-1866 | |
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