The HEDGEHOG-GLI1 pathway is important for fibroproliferative properties in keloids and as a candidate therapeutic target
Abstract Keloids are benign fibroproliferative skin tumors caused by aberrant wound healing that can negatively impact patient quality of life. The lack of animal models has limited research on pathogenesis or developing effective treatments, and the etiology of keloids remains unknown. Here, we fou...
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-12-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05561-z |
| _version_ | 1797397828654333952 |
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| author | Mamiko Tosa Yoshinori Abe Seiko Egawa Tomoka Hatakeyama Chihiro Iwaguro Ryotaro Mitsugi Ayaka Moriyama Takumi Sano Rei Ogawa Nobuyuki Tanaka |
| author_facet | Mamiko Tosa Yoshinori Abe Seiko Egawa Tomoka Hatakeyama Chihiro Iwaguro Ryotaro Mitsugi Ayaka Moriyama Takumi Sano Rei Ogawa Nobuyuki Tanaka |
| author_sort | Mamiko Tosa |
| collection | DOAJ |
| description | Abstract Keloids are benign fibroproliferative skin tumors caused by aberrant wound healing that can negatively impact patient quality of life. The lack of animal models has limited research on pathogenesis or developing effective treatments, and the etiology of keloids remains unknown. Here, we found that the characteristics of stem-like cells from keloid lesions and the surrounding dermis differ from those of normal skin. Furthermore, the HEDGEHOG (HH) signal and its downstream transcription factor GLI1 were upregulated in keloid patient–derived stem-like cells. Inhibition of the HH-GLI1 pathway reduced the expression of genes involved in keloids and fibrosis-inducing cytokines, including osteopontin. Moreover, the HH signal inhibitor vismodegib reduced keloid reconstituted tumor size and keloid-related gene expression in nude mice and the collagen bundle and expression of cytokines characteristic for keloids in ex vivo culture of keloid tissues. These results implicate the HH-GLI1 pathway in keloid pathogenesis and suggest therapeutic targets of keloids. |
| first_indexed | 2024-03-09T01:15:51Z |
| format | Article |
| id | doaj.art-a92b1da720804ee68c4542d1984c0cd3 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-09T01:15:51Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-a92b1da720804ee68c4542d1984c0cd32023-12-10T12:28:34ZengNature PortfolioCommunications Biology2399-36422023-12-016111610.1038/s42003-023-05561-zThe HEDGEHOG-GLI1 pathway is important for fibroproliferative properties in keloids and as a candidate therapeutic targetMamiko Tosa0Yoshinori Abe1Seiko Egawa2Tomoka Hatakeyama3Chihiro Iwaguro4Ryotaro Mitsugi5Ayaka Moriyama6Takumi Sano7Rei Ogawa8Nobuyuki Tanaka9Department of Molecular Oncology, Institute for Advanced Medical Sciences, Nippon Medical SchoolDepartment of Molecular Oncology, Institute for Advanced Medical Sciences, Nippon Medical SchoolDepartment of Molecular Oncology, Institute for Advanced Medical Sciences, Nippon Medical SchoolDepartment of Molecular Oncology, Institute for Advanced Medical Sciences, Nippon Medical SchoolDepartment of Molecular Oncology, Institute for Advanced Medical Sciences, Nippon Medical SchoolDepartment of Molecular Oncology, Institute for Advanced Medical Sciences, Nippon Medical SchoolDepartment of Molecular Oncology, Institute for Advanced Medical Sciences, Nippon Medical SchoolDepartment of Molecular Oncology, Institute for Advanced Medical Sciences, Nippon Medical SchoolDepartment of Plastic, Reconstructive and Aesthetic Surgery, Nippon Medical SchoolDepartment of Molecular Oncology, Institute for Advanced Medical Sciences, Nippon Medical SchoolAbstract Keloids are benign fibroproliferative skin tumors caused by aberrant wound healing that can negatively impact patient quality of life. The lack of animal models has limited research on pathogenesis or developing effective treatments, and the etiology of keloids remains unknown. Here, we found that the characteristics of stem-like cells from keloid lesions and the surrounding dermis differ from those of normal skin. Furthermore, the HEDGEHOG (HH) signal and its downstream transcription factor GLI1 were upregulated in keloid patient–derived stem-like cells. Inhibition of the HH-GLI1 pathway reduced the expression of genes involved in keloids and fibrosis-inducing cytokines, including osteopontin. Moreover, the HH signal inhibitor vismodegib reduced keloid reconstituted tumor size and keloid-related gene expression in nude mice and the collagen bundle and expression of cytokines characteristic for keloids in ex vivo culture of keloid tissues. These results implicate the HH-GLI1 pathway in keloid pathogenesis and suggest therapeutic targets of keloids.https://doi.org/10.1038/s42003-023-05561-z |
| spellingShingle | Mamiko Tosa Yoshinori Abe Seiko Egawa Tomoka Hatakeyama Chihiro Iwaguro Ryotaro Mitsugi Ayaka Moriyama Takumi Sano Rei Ogawa Nobuyuki Tanaka The HEDGEHOG-GLI1 pathway is important for fibroproliferative properties in keloids and as a candidate therapeutic target Communications Biology |
| title | The HEDGEHOG-GLI1 pathway is important for fibroproliferative properties in keloids and as a candidate therapeutic target |
| title_full | The HEDGEHOG-GLI1 pathway is important for fibroproliferative properties in keloids and as a candidate therapeutic target |
| title_fullStr | The HEDGEHOG-GLI1 pathway is important for fibroproliferative properties in keloids and as a candidate therapeutic target |
| title_full_unstemmed | The HEDGEHOG-GLI1 pathway is important for fibroproliferative properties in keloids and as a candidate therapeutic target |
| title_short | The HEDGEHOG-GLI1 pathway is important for fibroproliferative properties in keloids and as a candidate therapeutic target |
| title_sort | hedgehog gli1 pathway is important for fibroproliferative properties in keloids and as a candidate therapeutic target |
| url | https://doi.org/10.1038/s42003-023-05561-z |
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