PUBLICATION
Pannexin 1 drives efficient epithelial repair after tissue injury
- Authors
- Lucas, C.D., Medina, C.B., Bruton, F.A., Dorward, D.A., Raymond, M.H., Tufan, T., Etchegaray, J.I., Barron, B., Oremek, M.E.M., Arandjelovic, S., Farber, E., Onngut-Gumuscu, S., Ke, E., Whyte, M.K.B., Rossi, A.G., Ravichandran, K.S.
- ID
- ZDB-PUB-220514-62
- Date
- 2022
- Source
- Science immunology 7: eabm4032 (Journal)
- Registered Authors
- Lucas, Chris, Rossi, Adriano
- Keywords
- none
- MeSH Terms
-
- Animals
- Connexins*/genetics
- Connexins*/metabolism
- Epithelial Cells*/cytology
- Lung/metabolism
- Mice
- Neoplasm Proteins
- Nerve Tissue Proteins*/genetics
- Nerve Tissue Proteins*/metabolism
- Wounds and Injuries*
- Zebrafish
- PubMed
- 35559667 Full text @ Sci Immunol
Citation
Lucas, C.D., Medina, C.B., Bruton, F.A., Dorward, D.A., Raymond, M.H., Tufan, T., Etchegaray, J.I., Barron, B., Oremek, M.E.M., Arandjelovic, S., Farber, E., Onngut-Gumuscu, S., Ke, E., Whyte, M.K.B., Rossi, A.G., Ravichandran, K.S. (2022) Pannexin 1 drives efficient epithelial repair after tissue injury. Science immunology. 7:eabm4032.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping