The mechanotransducer Piezo1 coordinates metabolism and inflammation to promote skin growth
Yingchao Xue, Elizabeth Winnicki, Zhaoxu Zhang, Inés López, Saifeng Wang, Charles Kirby, Sam Lee, Ang Li, Chaewon Lee, Hana Minsky, Kaitlin L. Williams, Yueh‐Hsun Yang, Ling He, Sashank Reddy, Luis A. Garza
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. The skin has a remarkable ability to grow under stretch, though the underlying mechanisms remain unclear. Here, the authors show that the mechanosensor Piezo1 coordinates metabolic and immune responses to drive tension-induced skin growth.