Onset of re-epithelialization after skin injury correlates with a reorganization of keratin filaments in wound edge keratinocytes: defining a potential role for keratin 16.

TLDR

Injury to stratified epithelia triggers rapid induction of keratins 6 and 16 in post‑mitotic keratinocytes at the wound edge. The study proposes that K16 facilitates reorganization of the cytoplasmic keratin network, a prerequisite for keratinocyte migration during wound healing. K6 and K16 are induced within 6 h of injury, accumulate near the nucleus forming short filaments, and their reorganization into a juxtanuclear array coincides with re‑epithelialization at 18 h, while forced K16 expression in keratinocytes causes peripheral filament retraction, indicating K16’s role in cytoskeletal remodeling rather than structural support.

Abstract

Injury to stratified epithelia causes a strong induction of keratins 6 (K6) and 16 (K16) in post-mitotic keratinocytes located at the wound edge. We show that induction of K6 and K16 occurs within 6 h after injury to human epidermis. Their subsequent accumulation in keratinocytes correlates with the profound reorganization of keratin filaments from a pan-cytoplasmic distribution to one in which filaments are aggregated in a juxtanuclear location, opposite to the direction of cell migration. This filament reorganization coincides with additional cytoarchitectural changes and the onset of re-epithelialization after 18 h post-injury. By following the assembly of K6 and K16 in vitro and in cultured cells, we find that relative to K5 and K14, a well-characterized keratin pair that is constitutively expressed in epidermis, K6 and K16 polymerize into short 10-nm filaments that accumulate near the nucleus, a property arising from K16. Forced expression of human K16 in skin keratinocytes of transgenic mice causes a retraction of keratin filaments from the cell periphery, often in a polarized fashion. These results imply that K16 may not have a primary structural function akin to epidermal keratins. Rather, they suggest that in the context of epidermal wound healing, the function of K16 could be to promote a reorganization of the cytoplasmic array of keratin filaments, an event that precedes the onset of keratinocyte migration into the wound site.