The mechanotransducer Piezo1 coordinates metabolism and inflammation to promote skin growth
Abstract The skin has a remarkable ability to grow under constant stretch. Using a controlled tissue expansion system in mice, we identified an enhanced inflammatory-metabolic network in stretched skin via single-cell RNA sequencing, flow cytometry and spatial transcriptomics. Stretched epidermal ce...
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62270-3 |
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| author | Yingchao Xue Elizabeth Winnicki Zhaoxu Zhang Ines Lopez Saifeng Wang Charles Kirby Sam S. Lee Ang Li Chaewon Lee Hana Minsky Kaitlin Williams Kevin Yueh-Hsun Yang Ling He Sashank K. Reddy Luis A. Garza |
| author_facet | Yingchao Xue Elizabeth Winnicki Zhaoxu Zhang Ines Lopez Saifeng Wang Charles Kirby Sam S. Lee Ang Li Chaewon Lee Hana Minsky Kaitlin Williams Kevin Yueh-Hsun Yang Ling He Sashank K. Reddy Luis A. Garza |
| author_sort | Yingchao Xue |
| collection | DOAJ |
| description | Abstract The skin has a remarkable ability to grow under constant stretch. Using a controlled tissue expansion system in mice, we identified an enhanced inflammatory-metabolic network in stretched skin via single-cell RNA sequencing, flow cytometry and spatial transcriptomics. Stretched epidermal cells exhibit heightened cellular crosstalk of CXCL, CCL, TNF, and TGF-β signaling. Additionally, skin expansion increases macrophage and monocyte infiltration in the skin while altering systemic immune cell profiles. Glycolysis-related genes, including Glut1 and Aldoa were significantly elevated. We hypothesize that Piezo1, a non-selective calcium-permeable cation channel, senses tension in stretched skin, driving these responses. The epidermal-Piezo1 loss-of-function animals show reduced skin growth, tissue weight, tissue thickness, macrophage infiltration, and glycolysis activity. Conversely, animals with a pharmacological Piezo1 gain of function exhibit an increase in these factors. Our findings highlight the coordinating role of Piezo1 for metabolic changes and immune cell infiltration in tension-induced skin growth. |
| format | Article |
| id | doaj-art-a548bfb9c2d547d5ae6f564d16468267 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-a548bfb9c2d547d5ae6f564d164682672025-08-20T03:43:16ZengNature PortfolioNature Communications2041-17232025-07-0116111810.1038/s41467-025-62270-3The mechanotransducer Piezo1 coordinates metabolism and inflammation to promote skin growthYingchao Xue0Elizabeth Winnicki1Zhaoxu Zhang2Ines Lopez3Saifeng Wang4Charles Kirby5Sam S. Lee6Ang Li7Chaewon Lee8Hana Minsky9Kaitlin Williams10Kevin Yueh-Hsun Yang11Ling He12Sashank K. Reddy13Luis A. Garza14Department of Dermatology, Johns Hopkins UniversityDepartment of Dermatology, Johns Hopkins UniversityDepartment of Dermatology, Johns Hopkins UniversityDepartment of Dermatology, Johns Hopkins UniversityDepartment of Dermatology, Johns Hopkins UniversityDepartment of Dermatology, Johns Hopkins UniversityDepartment of Dermatology, Johns Hopkins UniversityDepartment of Dermatology, Johns Hopkins UniversityDepartment of Dermatology, Johns Hopkins UniversityDepartment of Dermatology, Johns Hopkins UniversityDepartment of Dermatology, Johns Hopkins UniversityDepartment of Plastic and Reconstructive Surgery, Johns Hopkins UniversityUniversity of Arizona College of Medicine-PhoenixDepartment of Plastic and Reconstructive Surgery, Johns Hopkins UniversityDepartment of Dermatology, Johns Hopkins UniversityAbstract The skin has a remarkable ability to grow under constant stretch. Using a controlled tissue expansion system in mice, we identified an enhanced inflammatory-metabolic network in stretched skin via single-cell RNA sequencing, flow cytometry and spatial transcriptomics. Stretched epidermal cells exhibit heightened cellular crosstalk of CXCL, CCL, TNF, and TGF-β signaling. Additionally, skin expansion increases macrophage and monocyte infiltration in the skin while altering systemic immune cell profiles. Glycolysis-related genes, including Glut1 and Aldoa were significantly elevated. We hypothesize that Piezo1, a non-selective calcium-permeable cation channel, senses tension in stretched skin, driving these responses. The epidermal-Piezo1 loss-of-function animals show reduced skin growth, tissue weight, tissue thickness, macrophage infiltration, and glycolysis activity. Conversely, animals with a pharmacological Piezo1 gain of function exhibit an increase in these factors. Our findings highlight the coordinating role of Piezo1 for metabolic changes and immune cell infiltration in tension-induced skin growth.https://doi.org/10.1038/s41467-025-62270-3 |
| spellingShingle | Yingchao Xue Elizabeth Winnicki Zhaoxu Zhang Ines Lopez Saifeng Wang Charles Kirby Sam S. Lee Ang Li Chaewon Lee Hana Minsky Kaitlin Williams Kevin Yueh-Hsun Yang Ling He Sashank K. Reddy Luis A. Garza The mechanotransducer Piezo1 coordinates metabolism and inflammation to promote skin growth Nature Communications |
| title | The mechanotransducer Piezo1 coordinates metabolism and inflammation to promote skin growth |
| title_full | The mechanotransducer Piezo1 coordinates metabolism and inflammation to promote skin growth |
| title_fullStr | The mechanotransducer Piezo1 coordinates metabolism and inflammation to promote skin growth |
| title_full_unstemmed | The mechanotransducer Piezo1 coordinates metabolism and inflammation to promote skin growth |
| title_short | The mechanotransducer Piezo1 coordinates metabolism and inflammation to promote skin growth |
| title_sort | mechanotransducer piezo1 coordinates metabolism and inflammation to promote skin growth |
| url | https://doi.org/10.1038/s41467-025-62270-3 |
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