Fibromodulin selectively accelerates myofibroblast apoptosis in cutaneous wounds by enhancing interleukin 1β signaling
Abstract Activated myofibroblasts deposit extracellular matrix material to facilitate rapid wound closure that can heal scarlessly during fetal development. However, adult myofibroblasts exhibit a relatively long life and persistent function, resulting in scarring. Thus, understanding how fetal and...
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| Language: | English |
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Nature Portfolio
2025-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58906-z |
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| author | Wenlu Jiang Xiaoxiao Pang Pin Ha Chenshuang Li Grace Xinlian Chang Yuxin Zhang Lawrence A. Bossong Kang Ting Chia Soo Zhong Zheng |
| author_facet | Wenlu Jiang Xiaoxiao Pang Pin Ha Chenshuang Li Grace Xinlian Chang Yuxin Zhang Lawrence A. Bossong Kang Ting Chia Soo Zhong Zheng |
| author_sort | Wenlu Jiang |
| collection | DOAJ |
| description | Abstract Activated myofibroblasts deposit extracellular matrix material to facilitate rapid wound closure that can heal scarlessly during fetal development. However, adult myofibroblasts exhibit a relatively long life and persistent function, resulting in scarring. Thus, understanding how fetal and adult tissue regeneration differs may serve to identify factors that promote more optimal wound healing in adults with little or less scarring. We previously found that matricellular proteoglycan fibromodulin is one such factor promoting more optimal repair, but the underlying molecular and cellular mechanisms for these effects have not been fully elucidated. Here, we find that fibromodulin induces myofibroblast apoptosis after wound closure to reduce scarring in small and large animal models. Mechanistically, fibromodulin accelerates and prolongs the formation of the interleukin 1β-interleukin 1 receptor type 1-interleukin 1 receptor accessory protein ternary complex to increase the apoptosis of myofibroblasts and keloid- and hypertrophic scar-derived cells. As the persistence of myofibroblasts during tissue regeneration is a key cause of fibrosis in most organs, fibromodulin represents a promising, broad-spectrum anti-fibrotic therapeutic. |
| format | Article |
| id | doaj-art-7264263ebc1b480abe84788bce6fbcc1 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-7264263ebc1b480abe84788bce6fbcc12025-08-20T03:10:07ZengNature PortfolioNature Communications2041-17232025-04-0116112010.1038/s41467-025-58906-zFibromodulin selectively accelerates myofibroblast apoptosis in cutaneous wounds by enhancing interleukin 1β signalingWenlu Jiang0Xiaoxiao Pang1Pin Ha2Chenshuang Li3Grace Xinlian Chang4Yuxin Zhang5Lawrence A. Bossong6Kang Ting7Chia Soo8Zhong Zheng9Division of Plastic and Reconstructive Surgery, David Geffen School of Medicine, University of California, Los AngelesChongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral, Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical UniversityDivision of Plastic and Reconstructive Surgery, David Geffen School of Medicine, University of California, Los AngelesDepartment of Orthodontics, School of Dental Medicine, University of PennsylvaniaDivision of Plastic and Reconstructive Surgery, David Geffen School of Medicine, University of California, Los AngelesChongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral, Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical UniversityDepartment of Neuroscience, Princeton UniversityAmerican Dental Association Forsyth InstituteDivision of Plastic and Reconstructive Surgery, David Geffen School of Medicine, University of California, Los AngelesDivision of Plastic and Reconstructive Surgery, David Geffen School of Medicine, University of California, Los AngelesAbstract Activated myofibroblasts deposit extracellular matrix material to facilitate rapid wound closure that can heal scarlessly during fetal development. However, adult myofibroblasts exhibit a relatively long life and persistent function, resulting in scarring. Thus, understanding how fetal and adult tissue regeneration differs may serve to identify factors that promote more optimal wound healing in adults with little or less scarring. We previously found that matricellular proteoglycan fibromodulin is one such factor promoting more optimal repair, but the underlying molecular and cellular mechanisms for these effects have not been fully elucidated. Here, we find that fibromodulin induces myofibroblast apoptosis after wound closure to reduce scarring in small and large animal models. Mechanistically, fibromodulin accelerates and prolongs the formation of the interleukin 1β-interleukin 1 receptor type 1-interleukin 1 receptor accessory protein ternary complex to increase the apoptosis of myofibroblasts and keloid- and hypertrophic scar-derived cells. As the persistence of myofibroblasts during tissue regeneration is a key cause of fibrosis in most organs, fibromodulin represents a promising, broad-spectrum anti-fibrotic therapeutic.https://doi.org/10.1038/s41467-025-58906-z |
| spellingShingle | Wenlu Jiang Xiaoxiao Pang Pin Ha Chenshuang Li Grace Xinlian Chang Yuxin Zhang Lawrence A. Bossong Kang Ting Chia Soo Zhong Zheng Fibromodulin selectively accelerates myofibroblast apoptosis in cutaneous wounds by enhancing interleukin 1β signaling Nature Communications |
| title | Fibromodulin selectively accelerates myofibroblast apoptosis in cutaneous wounds by enhancing interleukin 1β signaling |
| title_full | Fibromodulin selectively accelerates myofibroblast apoptosis in cutaneous wounds by enhancing interleukin 1β signaling |
| title_fullStr | Fibromodulin selectively accelerates myofibroblast apoptosis in cutaneous wounds by enhancing interleukin 1β signaling |
| title_full_unstemmed | Fibromodulin selectively accelerates myofibroblast apoptosis in cutaneous wounds by enhancing interleukin 1β signaling |
| title_short | Fibromodulin selectively accelerates myofibroblast apoptosis in cutaneous wounds by enhancing interleukin 1β signaling |
| title_sort | fibromodulin selectively accelerates myofibroblast apoptosis in cutaneous wounds by enhancing interleukin 1β signaling |
| url | https://doi.org/10.1038/s41467-025-58906-z |
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