Integrin and phosphotyrosine expression in normal and migrating newt keratinocytes

Abstract

The heavy accumulation of beta 1 and beta 4 at the wound bed interface in migrating cells suggests that these subunits may be involved in attachments of migrating cells to extracellular matrix proteins in the wound. The accumulation of ptyr in the same region further suggests that integrin-ligand interaction in keratinocytes modulates cell behavior through phosphorylated proteins. The fact that freshly isolated newt keratinocytes could adhere and spread on fibronectin or collagen shows that these cells are constitutively activated. This view is supported by the absence of any evidence that the beta 1 in migrating keratinocytes is larger and therefore more mature than beta 1 in normal keratinocytes. By comparison, beta 1 integrins on human keratinocytes are not constitutively activated (Takashima and Grinnell, 1985; Toda et al., 1987; Guo et al., 1990, 1991), a difference that may explain why epidermal wound healing is faster in newts than in humans.

Skin Regeneration in Adult Axolotls: A Blueprint for Scar-Free Healing in Vertebrates

“…This finding suggests that the transition from a pseudo-stratified to stratified epidermis following metamorphosis prevents rapid re-epithelialization in response to injury. Previous research in newt limbs suggested that epidermal keratinocytes are constitutively active and thus are primed to migrate following injury [24]. Our finding in paedomorphs supports this conclusion, while the observed delay in terrestrial axolotls demonstrates the need for keratinocyte activation as occurs in mammalian wound healing [57].…”

“…Observations from studies examining limb regeneration have been extrapolated to the skin, but direct comparisons to the processes of cutaneous wound repair have rarely been made [22]. Studies examining limb wounds have yielded insight into the process of re-epithelialization [23], [24], [25], [26] and regeneration of the basement membrane [27], [28], but the dynamics of dermal regeneration have remained obscure. Direct study of wound repair in urodele skin outside of regeneration fields like the limb and tail, however, has not been undertaken.…”

Integrin involvement in keratocyte locomotion

“…The ␤1 integrin co-localizes with a rim of close contact in the leading edge of locomoting fish keratocytes [Lee and Jacobson, 1997]. In a newt wound healing model [Donaldson et al, 1995], the ␤1 integrin has been found at the leading edge of cells migrating into the wound bed. Inhibition of the formation of ␤1 integrin-mediated adhesions at least partially elucidates the role of such adhesions in the coordination of protrusion and retraction necessary for forward movement of the cell.…”

“…Expression of integrins increases migration in a wound repair model [Danilenko et al, 1995] while decreasing integrin expression inhibits neuroblast migration in vivo [Galileo et al, 1992]. Furthermore, ␤1 integrins (and phosphotyrosine moieties) localize to the leading edge in wound closure [Donaldson et al, 1995] and inhibition of integrinmediated signaling doubles the time to wound closure [Romer et al, 1994].…”

Re‐epithelialization of large wound in paedomorphic and metamorphic axolotls

“…In the regenerative epidermis during limb regeneration in axolotls, expression microarray studies have revealed changing expression levels of several genes whose products are involved in cell adhesion or cell organization (Campbell et al, ). Constitutively high expression of β1‐ and β4‐ integrin subunits had been disclosed in normal and migrating newt epidermal cells (Donaldson et al, ). In contrast, in human epidermal cells β‐integrins are not constitutively activated (Guo et al, ).…”