CCL5 Induces a Sarcopenic-like Phenotype via the CCR5 Receptor
Sarcopenia corresponds to a decrease in muscle mass and strength. CCL5 is a new myokine whose expression, along with the CCR5 receptor, is increased in sarcopenic muscle. Therefore, we evaluated whether CCL5 and CCR5 induce a sarcopenic-like effect on skeletal muscle tissue and cultured muscle cells...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/14/1/84 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832589289178791936 |
|---|---|
| author | Francisco Aguirre Franco Tacchi Mayalen Valero-Breton Josué Orozco-Aguilar Sabrina Conejeros-Lillo Josefa Bonicioli Renata Iturriaga-Jofré Daniel Cabrera Jorge A. Soto Mauricio Castro-Sepúlveda Marianny Portal-Rodríguez Álvaro A. Elorza Andrea Matamoros Felipe Simon Claudio Cabello-Verrugio |
| author_facet | Francisco Aguirre Franco Tacchi Mayalen Valero-Breton Josué Orozco-Aguilar Sabrina Conejeros-Lillo Josefa Bonicioli Renata Iturriaga-Jofré Daniel Cabrera Jorge A. Soto Mauricio Castro-Sepúlveda Marianny Portal-Rodríguez Álvaro A. Elorza Andrea Matamoros Felipe Simon Claudio Cabello-Verrugio |
| author_sort | Francisco Aguirre |
| collection | DOAJ |
| description | Sarcopenia corresponds to a decrease in muscle mass and strength. CCL5 is a new myokine whose expression, along with the CCR5 receptor, is increased in sarcopenic muscle. Therefore, we evaluated whether CCL5 and CCR5 induce a sarcopenic-like effect on skeletal muscle tissue and cultured muscle cells. Electroporation in the tibialis anterior (TA) muscle of mice was used to overexpress CCL5. The TA muscles were analyzed by measuring the fiber diameter, the content of sarcomeric proteins, and the gene expression of E3-ligases. C<sub>2</sub>C<sub>12</sub> myotubes and single-isolated flexor digitorum brevis (FDB) fibers were also treated with recombinant CCL5 (rCCL5). The participation of CCR5 was evaluated using the antagonist maraviroc (MVC). Protein and structural analyses were performed. The results showed that TA overexpression of CCL5 led to sarcopenia by reducing muscle strength and mass, muscle-fiber diameter, and sarcomeric protein content, and by upregulating E3-ligases. The same sarcopenic phenotype was observed in myotubes and FDB fibers. We showed increased reactive oxygen species (ROS) production and carbonylated proteins, denoting oxidative stress induced by CCL5. When the CCR5 was antagonized, the effects produced by rCCL5 were prevented. In conclusion, we report for the first time that CCL5 is a novel myokine that exerts a sarcopenic-like effect through the CCR5 receptor. |
| format | Article |
| id | doaj-art-c22419e540714db595c0399a663b52bd |
| institution | Kabale University |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-c22419e540714db595c0399a663b52bd2025-01-24T13:19:26ZengMDPI AGAntioxidants2076-39212025-01-011418410.3390/antiox14010084CCL5 Induces a Sarcopenic-like Phenotype via the CCR5 ReceptorFrancisco Aguirre0Franco Tacchi1Mayalen Valero-Breton2Josué Orozco-Aguilar3Sabrina Conejeros-Lillo4Josefa Bonicioli5Renata Iturriaga-Jofré6Daniel Cabrera7Jorge A. Soto8Mauricio Castro-Sepúlveda9Marianny Portal-Rodríguez10Álvaro A. Elorza11Andrea Matamoros12Felipe Simon13Claudio Cabello-Verrugio14Laboratory of Muscle Pathology, Fragility and Aging, Department of Biological Sciences, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370146, ChileLaboratory of Muscle Pathology, Fragility and Aging, Department of Biological Sciences, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370146, ChileLaboratory of Muscle Pathology, Fragility and Aging, Department of Biological Sciences, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370146, ChileLaboratory of Muscle Pathology, Fragility and Aging, Department of Biological Sciences, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370146, ChileLaboratory of Muscle Pathology, Fragility and Aging, Department of Biological Sciences, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370146, ChileLaboratory of Muscle Pathology, Fragility and Aging, Department of Biological Sciences, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370146, ChileLaboratory of Muscle Pathology, Fragility and Aging, Department of Biological Sciences, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370146, ChileCentro de Investigación e Innovación Biomédica (CiiB), Universidad de los Andes, Santiago 7620001, ChileMillennium Institute on Immunology and Immunotherapy, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370146, ChileExercise Physiology and Metabolism Laboratory, School of Kinesiology, Faculty of Medicine, Finis Terrae University, Santiago 7501014, ChileLaboratory of Muscle Pathology, Fragility and Aging, Department of Biological Sciences, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370146, ChileInstitute of Biomedical Sciences, Faculty of Medicine and Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370071, ChileInstitute of Biomedical Sciences, Faculty of Medicine and Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370071, ChileMillennium Institute on Immunology and Immunotherapy, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370146, ChileLaboratory of Muscle Pathology, Fragility and Aging, Department of Biological Sciences, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370146, ChileSarcopenia corresponds to a decrease in muscle mass and strength. CCL5 is a new myokine whose expression, along with the CCR5 receptor, is increased in sarcopenic muscle. Therefore, we evaluated whether CCL5 and CCR5 induce a sarcopenic-like effect on skeletal muscle tissue and cultured muscle cells. Electroporation in the tibialis anterior (TA) muscle of mice was used to overexpress CCL5. The TA muscles were analyzed by measuring the fiber diameter, the content of sarcomeric proteins, and the gene expression of E3-ligases. C<sub>2</sub>C<sub>12</sub> myotubes and single-isolated flexor digitorum brevis (FDB) fibers were also treated with recombinant CCL5 (rCCL5). The participation of CCR5 was evaluated using the antagonist maraviroc (MVC). Protein and structural analyses were performed. The results showed that TA overexpression of CCL5 led to sarcopenia by reducing muscle strength and mass, muscle-fiber diameter, and sarcomeric protein content, and by upregulating E3-ligases. The same sarcopenic phenotype was observed in myotubes and FDB fibers. We showed increased reactive oxygen species (ROS) production and carbonylated proteins, denoting oxidative stress induced by CCL5. When the CCR5 was antagonized, the effects produced by rCCL5 were prevented. In conclusion, we report for the first time that CCL5 is a novel myokine that exerts a sarcopenic-like effect through the CCR5 receptor.https://www.mdpi.com/2076-3921/14/1/84sarcopeniaCCL5CCR5oxidative stressubiquitin–proteasome systemprotein synthesis |
| spellingShingle | Francisco Aguirre Franco Tacchi Mayalen Valero-Breton Josué Orozco-Aguilar Sabrina Conejeros-Lillo Josefa Bonicioli Renata Iturriaga-Jofré Daniel Cabrera Jorge A. Soto Mauricio Castro-Sepúlveda Marianny Portal-Rodríguez Álvaro A. Elorza Andrea Matamoros Felipe Simon Claudio Cabello-Verrugio CCL5 Induces a Sarcopenic-like Phenotype via the CCR5 Receptor Antioxidants sarcopenia CCL5 CCR5 oxidative stress ubiquitin–proteasome system protein synthesis |
| title | CCL5 Induces a Sarcopenic-like Phenotype via the CCR5 Receptor |
| title_full | CCL5 Induces a Sarcopenic-like Phenotype via the CCR5 Receptor |
| title_fullStr | CCL5 Induces a Sarcopenic-like Phenotype via the CCR5 Receptor |
| title_full_unstemmed | CCL5 Induces a Sarcopenic-like Phenotype via the CCR5 Receptor |
| title_short | CCL5 Induces a Sarcopenic-like Phenotype via the CCR5 Receptor |
| title_sort | ccl5 induces a sarcopenic like phenotype via the ccr5 receptor |
| topic | sarcopenia CCL5 CCR5 oxidative stress ubiquitin–proteasome system protein synthesis |
| url | https://www.mdpi.com/2076-3921/14/1/84 |
| work_keys_str_mv | AT franciscoaguirre ccl5inducesasarcopeniclikephenotypeviatheccr5receptor AT francotacchi ccl5inducesasarcopeniclikephenotypeviatheccr5receptor AT mayalenvalerobreton ccl5inducesasarcopeniclikephenotypeviatheccr5receptor AT josueorozcoaguilar ccl5inducesasarcopeniclikephenotypeviatheccr5receptor AT sabrinaconejeroslillo ccl5inducesasarcopeniclikephenotypeviatheccr5receptor AT josefabonicioli ccl5inducesasarcopeniclikephenotypeviatheccr5receptor AT renataiturriagajofre ccl5inducesasarcopeniclikephenotypeviatheccr5receptor AT danielcabrera ccl5inducesasarcopeniclikephenotypeviatheccr5receptor AT jorgeasoto ccl5inducesasarcopeniclikephenotypeviatheccr5receptor AT mauriciocastrosepulveda ccl5inducesasarcopeniclikephenotypeviatheccr5receptor AT mariannyportalrodriguez ccl5inducesasarcopeniclikephenotypeviatheccr5receptor AT alvaroaelorza ccl5inducesasarcopeniclikephenotypeviatheccr5receptor AT andreamatamoros ccl5inducesasarcopeniclikephenotypeviatheccr5receptor AT felipesimon ccl5inducesasarcopeniclikephenotypeviatheccr5receptor AT claudiocabelloverrugio ccl5inducesasarcopeniclikephenotypeviatheccr5receptor |