Celecoxib disrupts temporal coordination of TGF-β/α-SMA signaling in skeletal muscle repair: a time-dependent study of fibrosis and inflammation
Abstract Background The role of cyclooxygenase-2 (COX-2) inhibitors in skeletal muscle repair remains controversial due to their potential dual effects on inflammation and fibrosis. This study investigates the time-dependent impacts of the selective COX-2 inhibitor celecoxib on skeletal muscle regen...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-08-01
|
| Series: | European Journal of Medical Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40001-025-02996-4 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849388317858070528 |
|---|---|
| author | Jia Li Huan Chen Qianying Xiong Jinzhong Ni Fangyun Sun Xin Gong Huachun Miao |
| author_facet | Jia Li Huan Chen Qianying Xiong Jinzhong Ni Fangyun Sun Xin Gong Huachun Miao |
| author_sort | Jia Li |
| collection | DOAJ |
| description | Abstract Background The role of cyclooxygenase-2 (COX-2) inhibitors in skeletal muscle repair remains controversial due to their potential dual effects on inflammation and fibrosis. This study investigates the time-dependent impacts of the selective COX-2 inhibitor celecoxib on skeletal muscle regeneration, focusing on its modulation of α-smooth muscle actin (α-SMA), transforming growth factor-beta (TGF-β), and COX-2 pathways, to guide optimized therapeutic strategies. Methods Seventy-two C57BL/6 mice with blunt-impact gastrocnemius muscle injuries were divided into three groups: normal (no injury + saline), model (injury + saline), and celecoxib (injury + 100 mg/kg celecoxib). Tissue samples were collected at 3, 7, 14, and 21 days post-injury. Histopathological changes were assessed via hematoxylin–eosin (HE) and Masson staining. Molecular expression of α-SMA and TGF-β was analyzed by immunohistochemistry, COX-2 by immunofluorescence, and protein levels by Western blot. Results Celecoxib significantly reduced early-phase inflammation (3–7 days; P < 0.05) and fibrosis (P < 0.001) but delayed fibrosis resolution at 14–21 days. In the model group, α-SMA and TGF-β expression peaked at day 3 and day 7, respectively, followed by gradual declines. Celecoxib elevated α-SMA at day 3 (P < 0.05) but suppressed TGF-β from day 7 onward (P < 0.01). COX-2 expression was inhibited by celecoxib from day 3 to day 14 (P < 0.001), and α-SMA/TGF-β co-localization was disrupted, with minimal overlap after day 7. Conclusions Celecoxib mitigates early-phase inflammation, its prolonged use may compromise late-stage tissue maturation. These findings advocate for time-restricted administration of celecoxib in muscle injury therapy, emphasizing the need to balance acute symptom management with long-term functional recovery. |
| format | Article |
| id | doaj-art-1aed0c3cbc7c4ecba022141f66ce47b5 |
| institution | Kabale University |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj-art-1aed0c3cbc7c4ecba022141f66ce47b52025-08-20T03:42:20ZengBMCEuropean Journal of Medical Research2047-783X2025-08-0130111010.1186/s40001-025-02996-4Celecoxib disrupts temporal coordination of TGF-β/α-SMA signaling in skeletal muscle repair: a time-dependent study of fibrosis and inflammationJia Li0Huan Chen1Qianying Xiong2Jinzhong Ni3Fangyun Sun4Xin Gong5Huachun Miao6Department of Human Anatomy, Wannan Medical CollegeThe Second Affiliated Hospital of Wannan Medical CollegeDepartment of Human Anatomy, Wannan Medical CollegeDepartment of Human Anatomy, Wannan Medical CollegeSchool of Public Health, Wannan Medical CollegeDepartment of Human Anatomy, Wannan Medical CollegeDepartment of Human Anatomy, Wannan Medical CollegeAbstract Background The role of cyclooxygenase-2 (COX-2) inhibitors in skeletal muscle repair remains controversial due to their potential dual effects on inflammation and fibrosis. This study investigates the time-dependent impacts of the selective COX-2 inhibitor celecoxib on skeletal muscle regeneration, focusing on its modulation of α-smooth muscle actin (α-SMA), transforming growth factor-beta (TGF-β), and COX-2 pathways, to guide optimized therapeutic strategies. Methods Seventy-two C57BL/6 mice with blunt-impact gastrocnemius muscle injuries were divided into three groups: normal (no injury + saline), model (injury + saline), and celecoxib (injury + 100 mg/kg celecoxib). Tissue samples were collected at 3, 7, 14, and 21 days post-injury. Histopathological changes were assessed via hematoxylin–eosin (HE) and Masson staining. Molecular expression of α-SMA and TGF-β was analyzed by immunohistochemistry, COX-2 by immunofluorescence, and protein levels by Western blot. Results Celecoxib significantly reduced early-phase inflammation (3–7 days; P < 0.05) and fibrosis (P < 0.001) but delayed fibrosis resolution at 14–21 days. In the model group, α-SMA and TGF-β expression peaked at day 3 and day 7, respectively, followed by gradual declines. Celecoxib elevated α-SMA at day 3 (P < 0.05) but suppressed TGF-β from day 7 onward (P < 0.01). COX-2 expression was inhibited by celecoxib from day 3 to day 14 (P < 0.001), and α-SMA/TGF-β co-localization was disrupted, with minimal overlap after day 7. Conclusions Celecoxib mitigates early-phase inflammation, its prolonged use may compromise late-stage tissue maturation. These findings advocate for time-restricted administration of celecoxib in muscle injury therapy, emphasizing the need to balance acute symptom management with long-term functional recovery.https://doi.org/10.1186/s40001-025-02996-4Skeletal muscleContusionCelecoxibFibrosisInflammationCOX-2 |
| spellingShingle | Jia Li Huan Chen Qianying Xiong Jinzhong Ni Fangyun Sun Xin Gong Huachun Miao Celecoxib disrupts temporal coordination of TGF-β/α-SMA signaling in skeletal muscle repair: a time-dependent study of fibrosis and inflammation European Journal of Medical Research Skeletal muscle Contusion Celecoxib Fibrosis Inflammation COX-2 |
| title | Celecoxib disrupts temporal coordination of TGF-β/α-SMA signaling in skeletal muscle repair: a time-dependent study of fibrosis and inflammation |
| title_full | Celecoxib disrupts temporal coordination of TGF-β/α-SMA signaling in skeletal muscle repair: a time-dependent study of fibrosis and inflammation |
| title_fullStr | Celecoxib disrupts temporal coordination of TGF-β/α-SMA signaling in skeletal muscle repair: a time-dependent study of fibrosis and inflammation |
| title_full_unstemmed | Celecoxib disrupts temporal coordination of TGF-β/α-SMA signaling in skeletal muscle repair: a time-dependent study of fibrosis and inflammation |
| title_short | Celecoxib disrupts temporal coordination of TGF-β/α-SMA signaling in skeletal muscle repair: a time-dependent study of fibrosis and inflammation |
| title_sort | celecoxib disrupts temporal coordination of tgf β α sma signaling in skeletal muscle repair a time dependent study of fibrosis and inflammation |
| topic | Skeletal muscle Contusion Celecoxib Fibrosis Inflammation COX-2 |
| url | https://doi.org/10.1186/s40001-025-02996-4 |
| work_keys_str_mv | AT jiali celecoxibdisruptstemporalcoordinationoftgfbasmasignalinginskeletalmusclerepairatimedependentstudyoffibrosisandinflammation AT huanchen celecoxibdisruptstemporalcoordinationoftgfbasmasignalinginskeletalmusclerepairatimedependentstudyoffibrosisandinflammation AT qianyingxiong celecoxibdisruptstemporalcoordinationoftgfbasmasignalinginskeletalmusclerepairatimedependentstudyoffibrosisandinflammation AT jinzhongni celecoxibdisruptstemporalcoordinationoftgfbasmasignalinginskeletalmusclerepairatimedependentstudyoffibrosisandinflammation AT fangyunsun celecoxibdisruptstemporalcoordinationoftgfbasmasignalinginskeletalmusclerepairatimedependentstudyoffibrosisandinflammation AT xingong celecoxibdisruptstemporalcoordinationoftgfbasmasignalinginskeletalmusclerepairatimedependentstudyoffibrosisandinflammation AT huachunmiao celecoxibdisruptstemporalcoordinationoftgfbasmasignalinginskeletalmusclerepairatimedependentstudyoffibrosisandinflammation |