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Abstract
Epithelial tissues such as lung and skin are exposed to the environment and therefore particularly vulnerable to damage during injury or infection. Rapid repair is therefore essential to restore function and organ homeostasis. Dysregulated epithelial tissue repair occurs in several human disease states, yet how individual cell types communicate and interact to coordinate tissue regeneration is incompletely understood. Here, we show that pannexin 1 (Panx1), a cell membrane channel activated by caspases in dying cells, drives efficient epithelial regeneration after tissue injury by regulating injury-induced epithelial proliferation. Lung airway epithelial injury promotes the Panx1-dependent release of factors including ATP, from dying epithelial cells, which regulates macrophage phenotype after injury. This process, in turn, induces a reparative response in tissue macrophages that includes the induction of the soluble mitogen amphiregulin, which promotes injury-induced epithelial proliferation. Analysis of regenerating lung epithelium identified Panx1-dependent induction of Nras and Bcas2, both of which positively promoted epithelial proliferation and tissue regeneration in vivo. We also established that this role of Panx1 in boosting epithelial repair after injury is conserved between mouse lung and zebrafish tailfin. These data identify a Panx1-mediated communication circuit between epithelial cells and macrophages as a key step in promoting epithelial regeneration after injury.

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Citation

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MLA
Lucas, Christopher D., et al. “Pannexin 1 Drives Efficient Epithelial Repair after Tissue Injury.” SCIENCE IMMUNOLOGY, vol. 7, no. 71, 2022, doi:10.1126/sciimmunol.abm4032.
APA
Lucas, C. D., Medina, C. B., Bruton, F. A., Dorward, D. A., Raymond, M. H., Tufan, T., … Ravichandran, K. (2022). Pannexin 1 drives efficient epithelial repair after tissue injury. SCIENCE IMMUNOLOGY, 7(71). https://doi.org/10.1126/sciimmunol.abm4032
Chicago author-date
Lucas, Christopher D., Christopher B. Medina, Finnius A. Bruton, David A. Dorward, Michael H. Raymond, Turan Tufan, J. Iker Etchegaray, et al. 2022. “Pannexin 1 Drives Efficient Epithelial Repair after Tissue Injury.” SCIENCE IMMUNOLOGY 7 (71). https://doi.org/10.1126/sciimmunol.abm4032.
Chicago author-date (all authors)
Lucas, Christopher D., Christopher B. Medina, Finnius A. Bruton, David A. Dorward, Michael H. Raymond, Turan Tufan, J. Iker Etchegaray, Brady Barron, Magdalena E. M. Oremek, Sanja Arandjelovic, Emily Farber, Suna Onngut-Gumuscu, Eugene Ke, Moira K. B. Whyte, Adriano G. Rossi, and Kodi Ravichandran. 2022. “Pannexin 1 Drives Efficient Epithelial Repair after Tissue Injury.” SCIENCE IMMUNOLOGY 7 (71). doi:10.1126/sciimmunol.abm4032.
Vancouver
1.
Lucas CD, Medina CB, Bruton FA, Dorward DA, Raymond MH, Tufan T, et al. Pannexin 1 drives efficient epithelial repair after tissue injury. SCIENCE IMMUNOLOGY. 2022;7(71).
IEEE
[1]
C. D. Lucas et al., “Pannexin 1 drives efficient epithelial repair after tissue injury,” SCIENCE IMMUNOLOGY, vol. 7, no. 71, 2022.
@article{8760012,
  abstract     = {{Epithelial tissues such as lung and skin are exposed to the environment and therefore particularly vulnerable to damage during injury or infection. Rapid repair is therefore essential to restore function and organ homeostasis. Dysregulated epithelial tissue repair occurs in several human disease states, yet how individual cell types communicate and interact to coordinate tissue regeneration is incompletely understood. Here, we show that pannexin 1 (Panx1), a cell membrane channel activated by caspases in dying cells, drives efficient epithelial regeneration after tissue injury by regulating injury-induced epithelial proliferation. Lung airway epithelial injury promotes the Panx1-dependent release of factors including ATP, from dying epithelial cells, which regulates macrophage phenotype after injury. This process, in turn, induces a reparative response in tissue macrophages that includes the induction of the soluble mitogen amphiregulin, which promotes injury-induced epithelial proliferation. Analysis of regenerating lung epithelium identified Panx1-dependent induction of Nras and Bcas2, both of which positively promoted epithelial proliferation and tissue regeneration in vivo. We also established that this role of Panx1 in boosting epithelial repair after injury is conserved between mouse lung and zebrafish tailfin. These data identify a Panx1-mediated communication circuit between epithelial cells and macrophages as a key step in promoting epithelial regeneration after injury.}},
  articleno    = {{eabm4032}},
  author       = {{Lucas, Christopher D. and Medina, Christopher B. and Bruton, Finnius A. and Dorward, David A. and Raymond, Michael H. and Tufan, Turan and Etchegaray, J. Iker and Barron, Brady and Oremek, Magdalena E. M. and Arandjelovic, Sanja and Farber, Emily and Onngut-Gumuscu, Suna and Ke, Eugene and Whyte, Moira K. B. and Rossi, Adriano G. and Ravichandran, Kodi}},
  issn         = {{2470-9468}},
  journal      = {{SCIENCE IMMUNOLOGY}},
  language     = {{eng}},
  number       = {{71}},
  pages        = {{14}},
  title        = {{Pannexin 1 drives efficient epithelial repair after tissue injury}},
  url          = {{http://doi.org/10.1126/sciimmunol.abm4032}},
  volume       = {{7}},
  year         = {{2022}},
}

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