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.
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.
Paladini
R D
RD
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Takahashi
K
K
Bravo
N S
NS
Coulombe
P A
PA
D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004817:Epidermis / Q000473:pathology / Q000502:physiology; D004848:Epithelium / Q000502:physiology; D004926:Escherichia coli; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D007106:Immune Sera; D015603:Keratinocytes / Q000473:pathology / Q000502:physiology*; D007633:Keratins / Q000096:biosynthesis / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000648:ultrastructure; D012867:Skin / Q000293:injuries* / Q000473:pathology; D012879:Skin Physiological Phenomena; D014945:Wound Healing
D018076:DNA, Complementary; D007106:Immune Sera; D011994:Recombinant Proteins; D007633:Keratins