Mechanisms of epithelial wound detection

Abstract

Efficient wound healing requires the coordinated responses of various cell types within an injured tissue. To react to the presence of a wound, cells have to first detect it. Judging from their initial biochemical and morphological responses, many cells including leukocytes, epithelial and endothelial cells, detect wounds from over hundreds of micrometers within seconds-to-minutes. Wound detection involves the conversion of an injury-induced homeostatic perturbation, such as cell lysis, an unconstrained epithelial edge, or permeability barrier breakdown, into a chemical or physical signal. The signal is spatially propagated through the tissue to synchronize protective responses of cells near the wound site and at a distance. This review summarizes the triggers and mechanisms of wound detection in animals.

Zebrafish fin and heart: what's special about regeneration?

“…Reactive oxygen species (ROS) are important signaling molecules that are involved in the regulation of diverse biological processes [68]. After injury, wounds produce ROS, specifically hydrogen peroxide (H 2 O 2 ), which can form tissue-scale gradients and is required for early responses to wounding, in particular recruitment of immune cells [69]. Regeneration of tails in tadpoles of the frog Xenopus requires injury-induced ROS production [70].…”

“…Signals released by dying cells have long been recognized to mediate injury responses [69]. Interestingly however, in regenerating organs not just injury-induced cell death, but also programmed cell death actively induced by proregenerative signals might play an important role [72].…”

Image-Based Measurement of H 2 O 2 Reaction-Diffusion in Wounded Zebrafish Larvae

“…H 2 O 2 is a diffusible and relatively stable reactive oxygen species that may act as an early, paracrine wound signal during tissue inflammation and regeneration (1)(2)(3)(4)(5)(6)(7)(8). Tail fin tip amputation of larval zebrafish generates a tissue-scale gradient of H 2 O 2 through Ca 2þ -dependent activation of the epithelial NADPH oxidase Duox.…”

A Case for the Nuclear Membrane as a Mechanotransducer

“…Osmotic cell swelling after tail fin injury of zebrafish larvae is crucial for the recruitment of epithelial cells and leukocytes to the wound within minutes after injury. 10,11,17,31 Further more, nuclear deformations occur during 3D migration of cells through confined spaces, 7 e.g., when leukocytes squeeze their nuclei through narrow tissue channels on their way to injury or infection sites. 16 On a much slower timescale (i.e., hours-to-days), cell spreading or cell growth during the cell cycle also induce nuclear expansion.…”

“…2,41 Given the previous findings that PLA 2 -type phospholipases (and other membrane enzymes) are principally sensitive to membrane lipid packing density, this raises the intriguing possibility that the nuclear association of this central inflammatory pathway permits its mechanical regulation through nuclear membrane tension. 11,28 …”