Proliferation in murine epidermis after minor mechanical stimulation Part 1. Sustained increase in keratinocyte production and migration

Abstract

It was our objective to obtain an insight into the details and dynamics of the cell proliferative changes following minor barrier disruption, the mechanisms of recovery, and their regulation. Hair of the dorsal area of DBA2-mice was removed and the epidermis was tape stripped. Tritiated thymidine was injected into groups of mice at daily intervals thereafter. Labelling and nuclear densities were measured at several time intervals later in the various epidermal strata to characterize cell production and cell fluxes through the tissue. A dramatic proliferative response was observed at 24 h when the labelling density increased more than sixfold in the basal layer. Labelled cells rapidly appeared in suprabasal layers within a few hours in large quantities while this process took over 2 days in normal skin. Some cycling cells were also found in the suprabasal layer (pulse labelling at 24 h) in contrast with the controls. The cellular flux through the suprabasal layers was drastically (20-fold) increased and the transit time was shortened. Although the nuclear density in the basal layer showed only moderate changes it increased four-fold in the suprabasal layer within 5 days. A kinetic model analysis suggested that the cell cycle time of proliferative cells dropped from a normal value of about 200 h to less than 12 h post tape strip. After 7 days, the proliferative activation still persisted, even though at 3 days post tape strip the stratum corneum had been re-established. Hence, a mild mechanical alteration with removal of some parts of the cornified layer in mouse backskin epidermis triggers a huge proliferative response with massive overproduction of cells that lasts at least 7 days. Our findings suggest that the re-establishment of the cornified layer does not immediately shut down cell proliferation and that more complex, slower (long-term) regulatory processes are involved.

Cell kinetic studies in the murine ventral tongue epithelium: mucositis induced by radiation and its protection by pretreatment with keratinocyte growth factor (KGF)

“…The methods here are adopted from Potten et al (2000) and are described in Barthel et al (2002) and are based on a two-compartment model, the basal and suprabasal compartments with their cells. Provided that cell division occurs only in the basal layer and that cells are only labelled when in S, the increase in the number of labelled cells in the combined basal/suprabasal compartment, L tot is a measure of the cell production, whereas the increase in the suprabasal layer, L s is a measure of the cell migration from the basal to the suprabasal layer.…”

“… Cell production rate and migration rate at different times post irradiation as determined using the continuum model ( Potten et al. 2000 ; Barthel et al.…”

A continuum model to analyse spatial cell fluxes from positional labelling data applied to cell migration in oral mucosa

“…We also tried to estimate the basal cell production rate and basal cell turnover time with a method that we developed for the investigation of changes in the murine epidermis after a mechanical stimulus (Potten et al 2000). In this two-compartment approach, the steepness of the time course of the normalized number of labelled cells in the combined basal-suprabasal compartment is a measure of the cell production rate in the basal layer.…”

“…We also tried to estimate the basal cell production rate and basal cell turnover time with a method that we developed for the investigation of changes in the murine epidermis after a mechanical stimulus (Potten et al. 2000).…”

Proliferation in murine epidermis after minor mechanical stimulation Part 2. Alterations in keratinocyte cell cycle fluxes

“…We have recently performed a series of experiments on the effect of a mild mechanical irritation of the back skin of the mouse (Potten et al, 2000). It was our objective to obtain some further insight into the proliferation control mechanisms of the epidermis.…”