Piezo acts as a molecular brake on wound closure to ensure effective inflammation and maintenance of epithelial integrity

Luigi Zechini, Clelia Amato, Alessandro Scopelliti, Will Wood*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Wound healing entails a fine balance between re-epithelialization and inflammation1,2 so that the risk of infection is minimized, tissue architecture is restored without scarring, and the epithelium regains its ability to withstand mechanical forces. How the two events are orchestrated in vivo remains poorly understood, largely due to the experimental challenges of simultaneously addressing mechanical and molecular aspects of the damage response. Here, exploiting Drosophila's genetic tractability and live imaging potential, we uncover a dual role for Piezo-a mechanosensitive channel involved in calcium influx3-during re-epithelialization and inflammation following injury in vivo. We show that loss of Piezo leads to faster wound closure due to increased wound edge intercalation and exacerbated myosin cable heterogeneity. Moreover, we show that loss of Piezo leads to impaired inflammation due to lower epidermal calcium levels and, subsequently, insufficient damage-induced ROS production. Despite initially appearing beneficial, loss of Piezo is severely detrimental to the long-term effectiveness of repair. In fact, wounds inflicted on Piezo knockout embryos become a permanent point of weakness within the epithelium, leading to impaired barrier function and reduced ability of wounded embryos to survive. In summary, our study uncovers a role for Piezo in regulating epithelial cell dynamics and immune cell responsiveness during damage repair in vivo. We propose a model whereby Piezo acts as molecular brake during wound healing, slowing down closure to ensure activation of sustained inflammation and re-establishment of a fully functional epithelial barrier.
Original languageEnglish
Pages (from-to)3584-3592.e4
JournalCurrent Biology
Volume32
Issue number16
Early online date13 Jul 2022
DOIs
Publication statusPublished - 22 Aug 2022

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