Tight junction properties change during epidermis development

Abstract

In terrestrial animals, the epidermal barrier transitions from covering an organism suspended in a liquid environment in utero, to protecting a terrestrial animal postnatally from air and environmental exposure. Tight junctions (TJ) are essential for establishing the epidermal permeability barrier during embryonic development, and modulate normal epidermal development and barrier functions postnatally. We now report that TJ function, as well as claudin-1 and occludin expression, change in parallel during late epidermal development. Specifically, TJ block the paracellular movement of Lanthanum (La3+) early in rat in vivo prenatal epidermal development, at gestational days 18–19, with concurrent upregulation of claudin-1 and occludin. TJ then become more permeable to ions and water as the fetus approaches parturition, concomitant with development of the lipid epidermal permeability barrier, at days 20–21. This sequence is recapitulated in cultured human epidermal equivalents (HEE), as assessed both by ultrastructural studies comparing permeation of large and small molecules, and by the standard electrophysiologic parameter of resistance (R), suggesting further that this pattern of development is intrinsic to mammalian epidermal development. These findings demonstrate that the role of TJ changes during epidermal development, and further suggest that the TJ-based and lipid-based epidermal permeability barriers are interdependent.

Mechanisms of abnormal lamellar body secretion and the dysfunctional skin barrier in patients with atopic dermatitis

“…Transgenic knock-out of the key TJ protein, claudin 1, results in a fatal, post-natal permeability barrier abnormality 23 . Indeed, replete TJ are present early in epidermal development, but they become functionally incompetent later in fetal life in parallel with establishment of the lipid-based barrier 24 . An acquired reduction in the expression of the TJ protein, claudin 1, has been reported in AD 20 , and occludin protein levels decline in FLG-deficient human epidermis 25 .…”

Epidermal tight junctions in health and disease

“…Although several publications allude to an inside-out barrier to the electron dense ion tracer lanthanum in adult skin, 3,7,15,22 it is still challenging to distinguish whether this barrier property is from TJ or SC. 23 Studies investigating the outside-in barrier function of epidermal TJs are complicated by the close anatomical proximity of the SC, which prevents potential tracers from reaching the TJ barrier. However, the permeability/barrier function of TJs is bidirectional with the direction dependent from the molecules' gradient, thus if inside-out TJ barrier properties are shown the same should apply for their outside-in barrier property.…”

Nanotopography Facilitates in Vivo Transdermal Delivery of High Molecular Weight Therapeutics through an Integrin-Dependent Mechanism

“…However, recent studies have discovered the presence of the epidermal tight junction (TJ) and multiple TJ proteins, including occludin, zonula occludins-1 (ZO-1), and in particular claudins, which are critical for epidermal barrier function. 1–8 TJ complexes function as the paracellular barrier in simple epithelial cell types such as gastrointestinal mucosal cells and offer an additional well-conserved mechanism through which the skin can regulate its permeability. 9–11 While multiple technologies have attempted to increase the permeability of the stratum corneum, less emphasis has been placed on modulation of the skin TJ barrier.…”

“…This culture system forms stratified layers and tight junctions that recapitulate skin development in vivo . 1 Keratinocytes were allowed to develop to day 8, at which point they develop only a minimal stratum corneum layer. We elected this time point in order to provide a differentiated cell system that still enables maximal contact of the nanostructured film to the epidermal TJs, which lie beneath the stratum corneum layer of skin.…”