CILP1 interacting with YBX1 promotes hypertrophic scar formation by suppressing PPARs transcription
Abstract Hypertrophic scar (HS) represents the most prevalent form of skin fibrosis, significantly impacting the quality of life. Despite this, the molecular mechanisms driving HS formation remain largely undefined, impeding the development of effective treatments. The study showed that Cartilage In...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-05-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07554-8 |
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| author | Jianzhang Wang Juan Du Yajuan Song Xiaoying Tan Junzheng Wu Tong Wang Yi Shi Xingbo Xu Zhou Yu Baoqiang Song |
| author_facet | Jianzhang Wang Juan Du Yajuan Song Xiaoying Tan Junzheng Wu Tong Wang Yi Shi Xingbo Xu Zhou Yu Baoqiang Song |
| author_sort | Jianzhang Wang |
| collection | DOAJ |
| description | Abstract Hypertrophic scar (HS) represents the most prevalent form of skin fibrosis, significantly impacting the quality of life. Despite this, the molecular mechanisms driving HS formation remain largely undefined, impeding the development of effective treatments. The study showed that Cartilage Intermediate Layer Protein 1 (CILP1) was predominantly expressed in myofibroblasts and was up-regulated in various forms of skin fibrosis, including human hypertrophic and keloid scars, and in animal models of HS. Notably, we detected elevated serum levels of CILP1 in fifty-two patients with HS compared to twenty healthy individuals, suggesting its potential as a novel biomarker. The findings indicated that CILP1 was involved in a negative feedback loop with TGF-β and inhibited the transcription of Peroxisome Proliferator-Activated Receptors (PPARs) via interaction with Y-box-binding protein 1 (YBX1). This interaction promoted cell proliferation, migration, and collagen production in hypertrophic scar fibroblasts (HSFs). In vivo studies further confirmed that CILP1 knockdown markedly reduced HS formation, whereas administration of recombinant human CILP1 protein exacerbated it. These discoveries illuminated the CILP1-YBX1-PPARs signaling pathway as a key regulator of HS formation, offering a foundation for novel therapeutic approaches. |
| format | Article |
| id | doaj-art-266a34ce6bd04ddba9d7a747fb107aec |
| institution | OA Journals |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-266a34ce6bd04ddba9d7a747fb107aec2025-08-20T02:15:11ZengNature Publishing GroupCell Death and Disease2041-48892025-05-0116112210.1038/s41419-025-07554-8CILP1 interacting with YBX1 promotes hypertrophic scar formation by suppressing PPARs transcriptionJianzhang Wang0Juan Du1Yajuan Song2Xiaoying Tan3Junzheng Wu4Tong Wang5Yi Shi6Xingbo Xu7Zhou Yu8Baoqiang Song9Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University (Air Force Medical University)Department of Dermatology, Xuanwu Hospital, Capital Medical UniversityDepartment of Plastic Surgery, Xijing Hospital, Fourth Military Medical University (Air Force Medical University)Department of Nephrology and Rheumatology, University Medical Center Göttingen, Robert-Koch-Str. 40Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University (Air Force Medical University)Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University (Air Force Medical University)Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University (Air Force Medical University)Clinic for Cardiology and Pulmonology, University Medical Center Göttingen, Robert-Koch-Str. 40Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University (Air Force Medical University)Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University (Air Force Medical University)Abstract Hypertrophic scar (HS) represents the most prevalent form of skin fibrosis, significantly impacting the quality of life. Despite this, the molecular mechanisms driving HS formation remain largely undefined, impeding the development of effective treatments. The study showed that Cartilage Intermediate Layer Protein 1 (CILP1) was predominantly expressed in myofibroblasts and was up-regulated in various forms of skin fibrosis, including human hypertrophic and keloid scars, and in animal models of HS. Notably, we detected elevated serum levels of CILP1 in fifty-two patients with HS compared to twenty healthy individuals, suggesting its potential as a novel biomarker. The findings indicated that CILP1 was involved in a negative feedback loop with TGF-β and inhibited the transcription of Peroxisome Proliferator-Activated Receptors (PPARs) via interaction with Y-box-binding protein 1 (YBX1). This interaction promoted cell proliferation, migration, and collagen production in hypertrophic scar fibroblasts (HSFs). In vivo studies further confirmed that CILP1 knockdown markedly reduced HS formation, whereas administration of recombinant human CILP1 protein exacerbated it. These discoveries illuminated the CILP1-YBX1-PPARs signaling pathway as a key regulator of HS formation, offering a foundation for novel therapeutic approaches.https://doi.org/10.1038/s41419-025-07554-8 |
| spellingShingle | Jianzhang Wang Juan Du Yajuan Song Xiaoying Tan Junzheng Wu Tong Wang Yi Shi Xingbo Xu Zhou Yu Baoqiang Song CILP1 interacting with YBX1 promotes hypertrophic scar formation by suppressing PPARs transcription Cell Death and Disease |
| title | CILP1 interacting with YBX1 promotes hypertrophic scar formation by suppressing PPARs transcription |
| title_full | CILP1 interacting with YBX1 promotes hypertrophic scar formation by suppressing PPARs transcription |
| title_fullStr | CILP1 interacting with YBX1 promotes hypertrophic scar formation by suppressing PPARs transcription |
| title_full_unstemmed | CILP1 interacting with YBX1 promotes hypertrophic scar formation by suppressing PPARs transcription |
| title_short | CILP1 interacting with YBX1 promotes hypertrophic scar formation by suppressing PPARs transcription |
| title_sort | cilp1 interacting with ybx1 promotes hypertrophic scar formation by suppressing ppars transcription |
| url | https://doi.org/10.1038/s41419-025-07554-8 |
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