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

Abstract

We have recently shown that a mild mechanical irritation (tape strip) of the epidermis on the back skin of adult mice induces a strong and long lasting increase in proliferative activity and cell production. This was revealed by following the fate of 3HTdR-pulse labelled cells within the basal and suprabasal layers. To obtain further insight into the dynamics of cell kinetic changes we also performed double labelling experiments with 3HTdR and BrdUrd at various times after tape stripping. The technique for analysing the data had to account for a non stationary cell flux. A novel biometrical technique was developed which provides parameter estimates on the S-phase duration, the cell cycle duration and a parameter characterizing the degree of nonstationarity. When applied to the mechanically irritated epidermis we observed that the cell flux through the S-phase in the basal layer was accelerated by a factor of 10 between 18 and 36 h post tape strip. This activation declined slightly in the subsequent days and remained 4-6 fold higher than in the normal steady state for over 7 days post tape strip. The duration of the S-phase was 3-5 h and showed little variation. We conclude that mild mechanical irritation only affecting the stratum corneum has major stimulatory effects on the cell kinetics of proliferative keratinocytes in the basal layer of the epidermis indicating the existence of a powerful regulatory mechanism.

Characterization of the canine skin barrier restoration following acute disruption by tape stripping

“…29 The second phase is defined by increased lipid synthesis and by accelerated lamellar body formation and secretion, 30,31 leading to a slower decrease of TEWL value. During the third phase, increased keratinocyte proliferation 32 and differentiation complete the skin barrier recovery and the return of the TEWL value to normal. 6 In the present study, TEWL evolution presented the same type of pattern of recovery; a rapid decrease was observed within 24 h of recovery in all of the dogs and was followed by a slower decrease.…”

“…The second phase is defined by increased lipid synthesis and by accelerated lamellar body formation and secretion, 30,31 leading to a slower decrease of TEWL value. During the third phase, increased keratinocyte proliferation 32 and differentiation complete the skin barrier recovery and the return of the TEWL value to normal 6…”

Mechanical stretching modulates growth direction and MMP-9 release in human keratinocyte monolayer

“…21 A similar mechanism could act in our model as β1-integrin regulates MMP-9 mRNA stability 14 and MAPK activation induces MMP-9 expression in keratinocyte. 13,15 Moreover the mechanical stretching decreases cAMP and protein kinase A (PKA) activity in keratinocyte, 7 two biochemical signals that inhibit MMP-9 induction and cell migration. 22 Finally, in this paper, we evaluated only two MMPs, but keratinocyte migration is a composite mechanism that involves often different cell populations (e.g., dermal fibroblast) and different MMPs working in cooperation such as MT-MMP-1 and MMP-13 as clearly demonstrated in skin tumors.…”

“…4 In fact, mechanical pressure induce in vitro overexpression of differentiation markers in a keratinocyte cell line 5 reducing cell proliferation, 6 while the application of stretch seems to trigger keratinocyte growth and proliferation. 7,8 In particular, considering the uniaxial stretching, it has been pointed out that in human keratinocyte cyclic strain affects protein kinase C (PKC) activity, 9 increasing cell proliferation, DNA and protein synthesis 8,10 compared to stationary or constantly loaded cells, where mechanical stretching induces activation of MAPK extracellular signal regulated kinase ½ (ERK ½) via β1 integrin activation. 11 In this paper activation of cell migration in human keratinocyte monolayers by mechanical stretching has been evaluated measuring the monolayers area and orientation along with the production of MMP-9 and MMP-2, two proteolytic enzymes involved in the keratinocyte migration.…”

Organ culture and Reflectance Confocal Microscopy as new integrated tools for barrier rescue studies in inflammatory skin diseases

“…This phenomenon results in hyperkeratosis and parakeratosis, which ensure a rapid skin barrier repair (9) and act as regulatory mechanism that in turn stimulates basal layer proliferative kinetics (10). The presence of inflammatory-related marker modulation renders both TS and SDS models suitable for the study of the effect of immunomodulatory drugs in the context of skin barrier defects.…”