The mechanotransducer Piezo1 coordinates metabolism and inflammation to promote skin growth

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 () and Luis A. Garza ()
Additional contact information
Yingchao Xue: Johns Hopkins University
Elizabeth Winnicki: Johns Hopkins University
Zhaoxu Zhang: Johns Hopkins University
Ines Lopez: Johns Hopkins University
Saifeng Wang: Johns Hopkins University
Charles Kirby: Johns Hopkins University
Sam S. Lee: Johns Hopkins University
Ang Li: Johns Hopkins University
Chaewon Lee: Johns Hopkins University
Hana Minsky: Johns Hopkins University
Kaitlin Williams: Johns Hopkins University
Kevin Yueh-Hsun Yang: Johns Hopkins University
Ling He: University of Arizona College of Medicine-Phoenix
Sashank K. Reddy: Johns Hopkins University
Luis A. Garza: Johns Hopkins University

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-62270-3

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