Connexin hemichannels and early atrophic signaling in muscle during sepsis
Sepsis pathogenesis is complex, and effective treatments are limited, leading to high mortality rates between 20% and 55%. Early identification of factors contributing to sepsis-related muscle dysfunction is critical for risk stratification and potential therapeutic development. The immune response...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2025.1514769/full |
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| author | Elisa Balboa Fujiko Saavedra Luis A. Cea Aníbal A. Vargas Tomás Regueira Juan C. Sáez |
| author_facet | Elisa Balboa Fujiko Saavedra Luis A. Cea Aníbal A. Vargas Tomás Regueira Juan C. Sáez |
| author_sort | Elisa Balboa |
| collection | DOAJ |
| description | Sepsis pathogenesis is complex, and effective treatments are limited, leading to high mortality rates between 20% and 55%. Early identification of factors contributing to sepsis-related muscle dysfunction is critical for risk stratification and potential therapeutic development. The immune response during sepsis affects skeletal muscles, contributing to organ dysfunction and worsening prognosis. In this study, we explore the role of connexin hemichannels (Cx HCs) in the early changes in muscle homeostasis during sepsis. Using a cecal ligature and puncture (CLP)-induced sepsis model, we assessed IL-6 levels, weight loss, myofiber cross-sectional area, resting membrane potential, and connexin expression in control and Cx43/Cx45-deficient mice. CLP induced IL-6 elevation, sarcolemma permeabilization, reduced membrane potential, and activation of the ubiquitin–proteasome pathway in control mice, while Cx43/45-deficient mice exhibited reduced all CLP-induced muscle alterations. These findings suggest that Cx43 and Cx45 are involved in the early development of muscle alterations during sepsis. |
| format | Article |
| id | doaj-art-eb6b95bea10443619a07fe95f88a7d69 |
| institution | DOAJ |
| issn | 1664-042X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj-art-eb6b95bea10443619a07fe95f88a7d692025-08-20T02:45:02ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2025-02-011610.3389/fphys.2025.15147691514769Connexin hemichannels and early atrophic signaling in muscle during sepsisElisa Balboa0Fujiko Saavedra1Luis A. Cea2Aníbal A. Vargas3Tomás Regueira4Juan C. Sáez5Center for Biomedical Research, School of Medicine, Faculty of Medicine, Universidad Finis Terrae, Santiago, ChileProgram of Reproductive Biology, Research and Innovation Center, School of Medicine, Faculty of Medicine, Universidad de los Andes, Santiago, ChileInstituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago, ChileCenter for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, ChileIntensive Care Department, Clínica Santa María, Santiago, ChileInstituto de Neurociencias, Centro Interdisciplinario de Neurociencias de Valparaíso, Universidad de Valparaíso, Valparaíso, ChileSepsis pathogenesis is complex, and effective treatments are limited, leading to high mortality rates between 20% and 55%. Early identification of factors contributing to sepsis-related muscle dysfunction is critical for risk stratification and potential therapeutic development. The immune response during sepsis affects skeletal muscles, contributing to organ dysfunction and worsening prognosis. In this study, we explore the role of connexin hemichannels (Cx HCs) in the early changes in muscle homeostasis during sepsis. Using a cecal ligature and puncture (CLP)-induced sepsis model, we assessed IL-6 levels, weight loss, myofiber cross-sectional area, resting membrane potential, and connexin expression in control and Cx43/Cx45-deficient mice. CLP induced IL-6 elevation, sarcolemma permeabilization, reduced membrane potential, and activation of the ubiquitin–proteasome pathway in control mice, while Cx43/45-deficient mice exhibited reduced all CLP-induced muscle alterations. These findings suggest that Cx43 and Cx45 are involved in the early development of muscle alterations during sepsis.https://www.frontiersin.org/articles/10.3389/fphys.2025.1514769/fullresting membrane potentialmusclesinflammationchanneloapthyconnexin |
| spellingShingle | Elisa Balboa Fujiko Saavedra Luis A. Cea Aníbal A. Vargas Tomás Regueira Juan C. Sáez Connexin hemichannels and early atrophic signaling in muscle during sepsis Frontiers in Physiology resting membrane potential muscles inflammation channeloapthy connexin |
| title | Connexin hemichannels and early atrophic signaling in muscle during sepsis |
| title_full | Connexin hemichannels and early atrophic signaling in muscle during sepsis |
| title_fullStr | Connexin hemichannels and early atrophic signaling in muscle during sepsis |
| title_full_unstemmed | Connexin hemichannels and early atrophic signaling in muscle during sepsis |
| title_short | Connexin hemichannels and early atrophic signaling in muscle during sepsis |
| title_sort | connexin hemichannels and early atrophic signaling in muscle during sepsis |
| topic | resting membrane potential muscles inflammation channeloapthy connexin |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2025.1514769/full |
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