Differential Keratin Expression During Epiboly in a Wound Model of Bioengineered Skin and in Human Chronic Wounds

Abstract

Background Epiboly represents the process by which keratinocytes migrate to envelop a surface. We have been investigating a living bilayered skin construct (BSC) that is used in the treatment of lower extremity wounds due to venous insufficiency and diabetes. The construct demonstrates epiboly after injury and incubation in vitro, and this model may be useful for studying epidermal migration and the process of skin maturation. Punch biopsies of the construct in vitro were cultured and immunostained for specific keratins at baseline, and at 24–72 hours. For comparison, skin biopsy specimens from human chronic venous ulcers and acute healing wounds were similarly processed. We found that K1 and K10 were fully expressed in the epidermis of the fully epibolized surface on BSC. K1 was also present in the migrating edge of specimens, while K10 was not detectable. K16 and K6 were evident in normal skin and the epibolized area of the construct; K6 expression was very prominent in the migrating edge. Importantly, K17 was distinctly limited to the epibolized surface and the migrating edge, and its expression was very similar to that observed in healing human wounds. In conclusion, differential expression of keratins in this epiboly model closely reflects in vivo studies and supports keratin specificity in the processes of migration and differentiation of new epidermis. Therefore, these findings provide further and important validity for the study of epithelialization and the hope of developing prognostic markers for venous ulcer healing.

E3 Ligase Trim21 Ubiquitylates and Stabilizes Keratin 17 to Induce STAT3 Activation in Psoriasis

“…Keratin 17 (K17), a type I intermediate filament, provides structural support for keratinocytes to maintain the functional integrity of epidermis (Windoffer et al, 2011). Although it is undetectable in normal epidermis, K17 expression is elevated in hyperproliferative states such as psoriasis and wound healing (Coulombe, 1997;Leigh et al, 1995;Luo et al, 2011). The discrepancy in the tissue distribution of K17 between normal and psoriatic epidermis suggests that K17 is an indicator of keratinocyte hyperproliferation and can be considered as a hallmark of psoriasis.…”

Anin vitropriming step increases the expression of numerous epidermal growth and migration mediators in a tissue-engineering construct

“…Cell counts showed twice as many IL‐6‐positive cells in the primed BSC as compared to the unprimed. CK17, a keratin protein that is prominently expressed in migrating epidermis after injury (Luo et al ., ), was also detected in the epidermal keratinocytes (Figure d–f). It is initially confined to the migrating basal cells when the epidermis is 1–2 cells thick (Luo et al ., ).…”

“…CK17, a keratin protein that is prominently expressed in migrating epidermis after injury (Luo et al ., ), was also detected in the epidermal keratinocytes (Figure d–f). It is initially confined to the migrating basal cells when the epidermis is 1–2 cells thick (Luo et al ., ). In our study, it showed an almost exclusive suprabasal location in the unprimed BSC but was detectable in both basal and suprabasal cells in the primed construct.…”

“…Recognizing that there might be translational processes that are increased in priming, and without a detectable change in DNA levels, we also tested the tissue expression of CK17. This is a marker for epidermal proliferation/migration we recently found helpful (Luo et al ., ). Immunohistochemistry showed that, after priming, the BSC showed an increased expression of CK17.…”

Chitosan–poly(caprolactone) nanofibers for skin repair

“…Keratin 10 is a marker of keratinocyte differentiation and maturation, so lack of expression at the tip of a migratory epidermal tongue is indicative of the dedifferentiated state of cells at the leading edge [58] . The same pattern of keratin 10 expression (no expression at the leading edge of the epidermal tongue) is observed in the empty control group at days 10 and 14 as the migratory front advances across the wound bed under the scab (Figure 7e, i).…”