NRP1 transduces mechanical stress inhibition via LATS1/YAP in hypertrophic scars
Abstract Hypertrophic scar (HS) is an abnormal fibrous hyperplasia of the skin caused by excessive tissue repair in response to skin burns and trauma, which restricts physical function and impairs patients’ quality of life. Numerous studies have shown that pressure garment therapy (PGT) is an effect...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-09-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-023-01635-3 |
| _version_ | 1797578109126443008 |
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| author | Mengzhi Li Peng Wang Jingting Li Fei Zhou Shixin Huang Shaohai Qi Bin Shu |
| author_facet | Mengzhi Li Peng Wang Jingting Li Fei Zhou Shixin Huang Shaohai Qi Bin Shu |
| author_sort | Mengzhi Li |
| collection | DOAJ |
| description | Abstract Hypertrophic scar (HS) is an abnormal fibrous hyperplasia of the skin caused by excessive tissue repair in response to skin burns and trauma, which restricts physical function and impairs patients’ quality of life. Numerous studies have shown that pressure garment therapy (PGT) is an effective treatment for preventing hypertrophic scars. Herein, we found that mechanical stress stimulates the neuropilin 1 (NRP1) expression through screening GSE165027, GSE137210, and GSE120194 from Gene Expression Omnibus (GEO) database and bioinformatics analysis. We verified this stimulation in the human hypertrophic scar, pressure culture cell model, and rat tail-scar model. Mechanical compression increased LATS1 and pYAP enrichment, thus repressing the expression of YAP. Functionally, the knockdown of NRP1 promoted the expression of LATS1, thus decreasing the expression of YAP and inhibiting endothelial cell proliferation. Furthermore, co-immunoprecipitation analysis confirmed that NRP1 binds to YAP, and mechanical compression disrupted this binding, which resulted in the promotion of YAP relocation to nuclear. In conclusion, our results indicated that NRP1 transduces mechanical force inhibition by inhibiting YAP expression. Mechanical pressure can release YAP bound to NRP1, which explains the phenomenon that mechanical stress increases YAP in the nucleus. Strategies targeting NRP1 may promote compression therapy with optimal and comfortable pressures. |
| first_indexed | 2024-03-10T22:18:33Z |
| format | Article |
| id | doaj.art-958981677ec34271bd9f493b45eb5dce |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-03-10T22:18:33Z |
| publishDate | 2023-09-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-958981677ec34271bd9f493b45eb5dce2023-11-19T12:22:47ZengNature Publishing GroupCell Death Discovery2058-77162023-09-019111010.1038/s41420-023-01635-3NRP1 transduces mechanical stress inhibition via LATS1/YAP in hypertrophic scarsMengzhi Li0Peng Wang1Jingting Li2Fei Zhou3Shixin Huang4Shaohai Qi5Bin Shu6Department of Burns, the First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Burns, the First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Institute of Precision Medicine, the First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Burns, the First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Burns, the First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Burns, the First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Burns, the First Affiliated Hospital of Sun Yat-sen UniversityAbstract Hypertrophic scar (HS) is an abnormal fibrous hyperplasia of the skin caused by excessive tissue repair in response to skin burns and trauma, which restricts physical function and impairs patients’ quality of life. Numerous studies have shown that pressure garment therapy (PGT) is an effective treatment for preventing hypertrophic scars. Herein, we found that mechanical stress stimulates the neuropilin 1 (NRP1) expression through screening GSE165027, GSE137210, and GSE120194 from Gene Expression Omnibus (GEO) database and bioinformatics analysis. We verified this stimulation in the human hypertrophic scar, pressure culture cell model, and rat tail-scar model. Mechanical compression increased LATS1 and pYAP enrichment, thus repressing the expression of YAP. Functionally, the knockdown of NRP1 promoted the expression of LATS1, thus decreasing the expression of YAP and inhibiting endothelial cell proliferation. Furthermore, co-immunoprecipitation analysis confirmed that NRP1 binds to YAP, and mechanical compression disrupted this binding, which resulted in the promotion of YAP relocation to nuclear. In conclusion, our results indicated that NRP1 transduces mechanical force inhibition by inhibiting YAP expression. Mechanical pressure can release YAP bound to NRP1, which explains the phenomenon that mechanical stress increases YAP in the nucleus. Strategies targeting NRP1 may promote compression therapy with optimal and comfortable pressures.https://doi.org/10.1038/s41420-023-01635-3 |
| spellingShingle | Mengzhi Li Peng Wang Jingting Li Fei Zhou Shixin Huang Shaohai Qi Bin Shu NRP1 transduces mechanical stress inhibition via LATS1/YAP in hypertrophic scars Cell Death Discovery |
| title | NRP1 transduces mechanical stress inhibition via LATS1/YAP in hypertrophic scars |
| title_full | NRP1 transduces mechanical stress inhibition via LATS1/YAP in hypertrophic scars |
| title_fullStr | NRP1 transduces mechanical stress inhibition via LATS1/YAP in hypertrophic scars |
| title_full_unstemmed | NRP1 transduces mechanical stress inhibition via LATS1/YAP in hypertrophic scars |
| title_short | NRP1 transduces mechanical stress inhibition via LATS1/YAP in hypertrophic scars |
| title_sort | nrp1 transduces mechanical stress inhibition via lats1 yap in hypertrophic scars |
| url | https://doi.org/10.1038/s41420-023-01635-3 |
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