Normal and Gene-Corrected Dystrophic Epidermolysis Bullosa Fibroblasts Alone Can Produce Type VII Collagen at the Basement Membrane Zone

David T Woodley; Tom Atha; Yi Huang; Mei Chen; Gerald G Krueger; Cynthia M Jorgensen; Janet A Fairley; Lawrence Chan; Douglas R Keene

doi:10.1046/j.1523-1747.2003.12571.x

Back

Normal and Gene-Corrected Dystrophic Epidermolysis Bullosa Fibroblasts Alone Can Produce Type VII Collagen at the Basement Membrane Zone

Journal article

Open access

Peer reviewed

Normal and Gene-Corrected Dystrophic Epidermolysis Bullosa Fibroblasts Alone Can Produce Type VII Collagen at the Basement Membrane Zone

David T Woodley, Tom Atha, Yi Huang, Mei Chen, Gerald G Krueger, Cynthia M Jorgensen, Janet A Fairley, Lawrence Chan and Douglas R Keene

Journal of investigative dermatology, Vol.121(5), pp.1021-1028

11/2003

DOI: 10.1046/j.1523-1747.2003.12571.x

PMID: 14708601

Files and links (1)

url

https://doi.org/10.1046/j.1523-1747.2003.12571.xView

Published (Version of record) Open Access

Abstract

Type VII collagen is synthesized and secreted by both human keratinocytes and fibroblasts. Although both cell types can secrete type VII collagen, it is thought that keratinocytes account for type VII collagen at the dermal–epidermal junction (DEJ). In this study, we examined if type VII collagen secreted solely by dermal fibroblasts could be transported to the DEJ. We established organotypic, skin-equivalent cultures composed of keratinocytes from patients with recessive dystrophic epidermolysis bullosa (RDEB) and normal dermal fibroblasts. Immuno-labeling of skin equivalent sections with the anti-type VII collagen antibody revealed tight linear staining at the DEJ. RDEB fibroblasts, were gene-corrected to make type VII collagen and used to regenerate human skin on immune-deficient mice. The human skin generated by gene-corrected RDEB fibroblasts or normal human fibroblasts combined with RDEB keratinocytes restored type VII collagen expression at the DEJ in vivo. Further, intradermal injection of normal human or gene-corrected RDEB fibroblasts into mouse skin resulted in the stable expression of human type VII collagen at the mouse DEJ. These data demonstrate that human dermal fibroblasts alone are capable of producing type VII collagen at the DEJ, and it is possible to restore type VII collagen gene expression in RDEB skin in vivo by direct intradermal injection of fibroblasts.

Details

Title: Subtitle: Normal and Gene-Corrected Dystrophic Epidermolysis Bullosa Fibroblasts Alone Can Produce Type VII Collagen at the Basement Membrane Zone
Creators: David T Woodley
Tom Atha
Yi Huang
Mei Chen
Gerald G Krueger - Departments of Dermatology, University of Utah Health Science Center, Salt Lake City, Utah
Cynthia M Jorgensen - Departments of Dermatology, University of Utah Health Science Center, Salt Lake City, Utah
Janet A Fairley - Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Lawrence Chan - University of Illinois College of Medicine, Chicago, Illinois
Douglas R Keene - Shriners Hospital for Children, Portland, Oregon
Resource Type: Journal article
Publication Details: Journal of investigative dermatology, Vol.121(5), pp.1021-1028
Publisher: Elsevier Inc
DOI: 10.1046/j.1523-1747.2003.12571.x
PMID: 14708601
ISSN: 0022-202X
eISSN: 1523-1747
Language: English
Date published: 11/2003
Academic Unit: Dermatology
Record Identifier: 9984025581502771

Metrics

16 Record Views

97 Times Cited - Web of Science

See more details