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

doi:10.1083/jcb.132.3.381

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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

RD Paladini, K Takahashi, NS Bravo and PA Coulombe
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

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.
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Cao, Z., Wu, H. K., Bruce, A., Wollenberg, K., Panjwani, N. (2002). Detection of Differentially Expressed Genes in Healing Mouse Corneas, Using cDNA Microarrays. IOVS 43: 2897-2904 [Abstract] [Full Text]
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Chou, Y.-H., Goldman, R. D. (2000). Intermediate Filaments on the Move. JCB 150: 101-106 [Full Text]
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Pekny, M., Johansson, C. B., Eliasson, C., Stakeberg, J., Wallen, A., Perlmann, T., Lendahl, U., Betsholtz, C., Berthold, C.-H., Frisen, J. (1999). Abnormal Reaction to Central Nervous System Injury in Mice Lacking Glial Fibrillary Acidic Protein and Vimentin. JCB 145: 503-514 [Abstract] [Full Text]
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Thacher, S. M., Nagpal, S., Klein, E. S., Arefieg, T., Krasinski, G., DiSepio, D., Agarwal, C., Johnson, A., Eckert, R. L., Chandraratna, R. A. S. (1999). Cell Type and Gene-specific Activity of the Retinoid Inverse Agonist AGN 193109: Divergent Effects from Agonist at Retinoic Acid Receptor {{gamma}} in Human Keratinocytes. Cell Growth Differ. 10: 255-262 [Abstract] [Full Text]
Goldfinger, L., Hopkinson, S., deHart, G., Collawn, S, Couchman, J., Jones, J. (1999). The alpha3 laminin subunit, alpha6beta4 and alpha3beta1 integrin coordinately regulate wound healing in cultured epithelial cells and in the skin. J. Cell Sci. 112: 2615-2629 [Abstract]
Fradette, J., Germain, L., Seshaiah, P., Coulombe, P. A. (1998). The Type I Keratin 19�Possesses Distinct and Context-dependent Assembly Properties. J. Biol. Chem. 273: 35176-35184 [Abstract] [Full Text]
Porter, R. M., Hutcheson, A. M., Rugg, E. L., Quinlan, R. A., Lane, E. B. (1998). cDNA Cloning, Expression, and Assembly Characteristics of Mouse Keratin 16. J. Biol. Chem. 273: 32265-32272 [Abstract] [Full Text]
Laplante, A. F., Moulin, V., Auger, F. A., Landry, J., Li, H., Morrow, G., Tanguay, R. M., Germain, L. (1998). Expression of Heat Shock Proteins in Mouse Skin During Wound Healing. J. Histochem. Cytochem. 46: 1291-1302 [Abstract] [Full Text]
McGowan, K. M., Coulombe, P. A. (1998). Onset of Keratin 17 Expression Coincides with the Definition of Major Epithelial Lineages during Skin Development. JCB 143: 469-486 [Abstract] [Full Text]
Hutton, E., Paladini, R. D., Yu, Q.-C., Yen, M., Coulombe, P. A., Fuchs, E. (1998). Functional Differences between Keratins of Stratified and Simple Epithelia. JCB 143: 487-499 [Abstract] [Full Text]
Paladini, R. D., Coulombe, P. A. (1998). Directed Expression of Keratin 16 to the Progenitor Basal Cells of Transgenic Mouse Skin Delays Skin Maturation. JCB 142: 1035-1051 [Abstract] [Full Text]
Magin, T. M., Schroder, R., Leitgeb, S., Wanninger, F., Zatloukal, K., Grund, C., Melton, D. W. (1998). Lessons from Keratin 18 Knockout Mice: Formation of Novel Keratin Filaments, Secondary Loss of Keratin 7 and Accumulation of Liver-specific Keratin 8-Positive Aggregates. JCB 140: 1441-1451 [Abstract] [Full Text]
Wawersik, M., Paladini, R. D., Noensie, E., Coulombe, P. A. (1997). A Proline Residue in the alpha -Helical Rod Domain of Type I Keratin 16�Destabilizes Keratin Heterotetramers. J. Biol. Chem. 272: 32557-32565 [Abstract] [Full Text]
Andersen, B, Weinberg, W C, Rennekampff, O, McEvilly, R J, Bermingham, J R, Hooshmand, F, Vasilyev, V, Hansbrough, J F, Pittelkow, M R, Yuspa, S H, Rosenfeld, M G (1997). Functions of the POU domain genes Skn-1a/i and Tst-1/Oct-6/SCIP in epidermal differentiation.. Genes Dev. 11: 1873-1884 [Abstract]
Takahashi, K., Coulombe, P. A. (1997). Defining a Region of the Human Keratin 6a Gene That Confers Inducible Expression in Stratified Epithelia of Transgenic Mice. J. Biol. Chem. 272: 11979-11985 [Abstract] [Full Text]
Martin, P. (1997). Wound Healing--Aiming for Perfect Skin Regeneration. Science 276: 75-81 [Abstract] [Full Text]
Reichelt, J, Bauer, C, Porter, R, Lane, E, Magin, V (1997). Out of balance: consequences of a partial keratin 10 knockout. J. Cell Sci. 110: 2175-2186 [Abstract]
Paramio, J., Casanova, M., Alonso, A, Jorcano, J. (1997). Keratin intermediate filament dynamics in cell heterokaryons reveals diverse behaviour of different keratins. J. Cell Sci. 110: 1099-1111 [Abstract]
Takahashi, K., Coulombe, P.�A. (1996). A transgenic mouse model with an inducible skin blistering disease�phenotype. Proc. Natl. Acad. Sci. USA 93: 14776-14781 [Abstract] [Full Text]
Spradling, K. D., McDaniel, A. E., Lohi, J., Pilcher, B. K. (2001). Epsin 3 Is a Novel Extracellular Matrix-induced Transcript Specific to Wounded Epithelia. J. Biol. Chem. 276: 29257-29267 [Abstract] [Full Text]