Loss of Keratin 6 (K6) Proteins Reveals a Function for Intermediate Filaments during Wound Repair
The ability to heal wounds is vital to all organisms. In mammalian tissues, alterations in intermediate filament (IF) gene expression represent an early reaction of cells surviving injury. We investigated the role of keratin IFs during the epithelialization of skin wounds using a keratin 6α and 6β (...
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| Published in | The Journal of cell biology Vol. 163; no. 2; pp. 327 - 337 |
|---|---|
| Main Authors | , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Rockefeller University Press
27.10.2003
The Rockefeller University Press |
| Subjects | |
| Online Access | Get full text |
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| Abstract | The ability to heal wounds is vital to all organisms. In mammalian tissues, alterations in intermediate filament (IF) gene expression represent an early reaction of cells surviving injury. We investigated the role of keratin IFs during the epithelialization of skin wounds using a keratin 6α and 6β (K6α/K6β)-null mouse model. In skin explant culture, null keratinocytes exhibit an enhanced epithelialization potential due to increased migration. The extent of the phenotype is strain dependent, and is accompanied by alterations in keratin IF and F-actin organization. However, in wounded skin in vivo, null keratinocytes rupture as they attempt to migrate under the blood clot. Fragility of the K6α/K6β-null epidermis is confirmed when applying trauma to chemically treated skin. We propose that the alterations in IF gene expression after tissue injury foster a compromise between the need to display the cellular pliability necessary for timely migration and the requirement for resilience sufficient to withstand the rigors of a wound site. |
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| AbstractList | The ability to heal wounds is vital to all organisms. In mammalian tissues, alterations in intermediate filament (IF) gene expression represent an early reaction of cells surviving injury. We investigated the role of keratin IFs during the epithelialization of skin wounds using a keratin 6α and 6β (K6α/K6β)-null mouse model. In skin explant culture, null keratinocytes exhibit an enhanced epithelialization potential due to increased migration. The extent of the phenotype is strain dependent, and is accompanied by alterations in keratin IF and F-actin organization. However, in wounded skin in vivo, null keratinocytes rupture as they attempt to migrate under the blood clot. Fragility of the K6α/K6β-null epidermis is confirmed when applying trauma to chemically treated skin. We propose that the alterations in IF gene expression after tissue injury foster a compromise between the need to display the cellular pliability necessary for timely migration and the requirement for resilience sufficient to withstand the rigors of a wound site. The ability to heal wounds is vital to all organisms. In mammalian tissues, alterations in intermediate filament (IF) gene expression represent an early reaction of cells surviving injury. We investigated the role of keratin IFs during the epithelialization of skin wounds using a keratin 6alpha and 6beta (K6alpha/K6beta)-null mouse model. In skin explant culture, null keratinocytes exhibit an enhanced epithelialization potential due to increased migration. The extent of the phenotype is strain dependent, and is accompanied by alterations in keratin IF and F-actin organization. However, in wounded skin in vivo, null keratinocytes rupture as they attempt to migrate under the blood clot. Fragility of the K6alpha/K6beta-null epidermis is confirmed when applying trauma to chemically treated skin. We propose that the alterations in IF gene expression after tissue injury foster a compromise between the need to display the cellular pliability necessary for timely migration and the requirement for resilience sufficient to withstand the rigors of a wound site. The ability to heal wounds is vital to all organisms. In mammalian tissues, alterations in intermediate filament (IF) gene expression represent an early reaction of cells surviving injury. We investigated the role of keratin IFs during the epithelialization of skin wounds using a keratin 6{alpha} and 6 Beta (K6{alpha}/K6 Beta)-null mouse model. In skin explant culture, null keratinocytes exhibit an enhanced epithelialization potential due to increased migration. The extent of the phenotype is strain dependent, and is accompanied by alterations in keratin IF and F-actin organization. However, in wounded skin in vivo, null keratinocytes rupture as they attempt to migrate under the blood clot. Fragility of the K6{alpha}/K6 Beta-null epidermis is confirmed when applying trauma to chemically treated skin. We propose that the alterations in IF gene expression after tissue injury foster a compromise between the need to display the cellular pliability necessary for timely migration and the requirement for resilience sufficient to withstand the rigors of a wound site. [PUBLICATION ABSTRACT] The ability to heal wounds is vital to all organisms. In mammalian tissues, alterations in intermediate filament (IF) gene expression represent an early reaction of cells surviving injury. We investigated the role of keratin IFs during the epithelialization of skin wounds using a keratin 6 alpha and 6 beta (K6 alpha /K6 beta )-null mouse model. In skin explant culture, null keratinocytes exhibit an enhanced epithelialization potential due to increased migration. The extent of the phenotype is strain dependent, and is accompanied by alterations in keratin IF and F-actin organization. However, in wounded skin in vivo, null keratinocytes rupture as they attempt to migrate under the blood clot. Fragility of the K6 alpha /K6 beta -null epidermis is confirmed when applying trauma to chemically treated skin. We propose that the alterations in IF gene expression after tissue injury foster a compromise between the need to display the cellular pliability necessary for timely migration and the requirement for resilience sufficient to withstand the rigors of a wound site. |
| Author | Wong, Pauline Coulombe, Pierre A. |
| AuthorAffiliation | 1 Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 2 Department of Dermatology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 |
| AuthorAffiliation_xml | – name: 2 Department of Dermatology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 – name: 1 Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 |
| Author_xml | – sequence: 1 givenname: Pauline surname: Wong fullname: Wong, Pauline – sequence: 2 givenname: Pierre A. surname: Coulombe fullname: Coulombe, Pierre A. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/14568992$$D View this record in MEDLINE/PubMed |
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| Copyright | Copyright 2003 The Rockefeller University Press Copyright Rockefeller University Press Oct 27, 2003 Copyright © 2003, The Rockefeller University Press |
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| Notes | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 Address correspondence to Pierre A. Coulombe, Dept. of Biological Chemistry, The Johns Hopkins University School of Medicine, 725 North Wolfe St., Baltimore, MD 21205. Tel.: (410) 614-0510. Fax: (410) 614-7567. email: coulombe@jhmi.edu Abbreviations used in this paper: CNS, central nervous system; GFAP, glial fibrillary acidic protein; H&E, hematoxylin and eosin; IF, intermediate filament. |
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| Snippet | The ability to heal wounds is vital to all organisms. In mammalian tissues, alterations in intermediate filament (IF) gene expression represent an early... |
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| SubjectTerms | Actins Animals Cell Movement - physiology Cells, Cultured Cellular biology Epidermis Epithelial cells Gene Expression Gene expression regulation Injuries Intermediate filaments Intermediate Filaments - metabolism Keratinocytes Keratinocytes - cytology Keratinocytes - physiology Keratins Keratins - genetics Keratins - metabolism Keratins - physiology Mice Mice, Inbred C57BL Mice, Knockout Mice, Nude Mutation Organ Culture Techniques Physical trauma Proteins Skin Skin - cytology Skin - metabolism Transplantation, Homologous Transplants Wound Healing - physiology |
| Title | Loss of Keratin 6 (K6) Proteins Reveals a Function for Intermediate Filaments during Wound Repair |
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