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

• Published in: Current biology 2022-08, Vol.32 (16), p.3584-3592.e4
• Main Authors: Zechini, Luigi, Amato, Clelia, Scopelliti, Alessandro, Wood, Will
• Format: Article
• Language: English
• Subjects: Calcium; Drosophila; Epidermis; epithelial resilience; Epithelium; Humans; Inflammation; Piezo; ROS; wound healing; Wound Healing - genetics
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2022.06.041

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. [Display omitted] •Loss of Piezo accelerates wound closure and weakens inflammation in vivo•Loss of Piezo enhances wound edge cell intercalation and myosin cable heterogeneity•Loss of Piezo reduces epidermal Ca++ levels and damage-induced ROS production•Loss of Piezo compromises post-wounding epithelial barrier function and survival Zechini et al. have shown that the mechanosensitive channel Piezo delays wound closure by limiting myosin cable heterogeneity and wound edge cell intercalation, while also ensuring a sustained inflammatory response. Piezo is essential for efficient restoration of epithelial barrier function and to ensure post-wound survival in vivo.