Research Paper Volume 7, Issue 6 pp 389—411

Transcriptome and ultrastructural changes in dystrophic Epidermolysis bullosa resemble skin aging

Jenny S. Breitenbach1, *, , Mark Rinnerthaler2, *, , Andrea Trost3, , Manuela Weber2, , Alfred Klausegger1, , Christina Gruber1, , Daniela Bruckner3, , Herbert A. Reitsamer3, , Johann W. Bauer1, , Michael Breitenbach2, ,

  • 1 Department of Dermatology and EB House Austria, Paracelsus Medical University, Salzburg, Austria
  • 2 Fachbereich Zellbiologie der Universität Salzburg, Salzburg, Austria
  • 3 University Clinic of Ophthalmology and Optometry, Research Program for Ophthalmology and Glaucoma Research, Paracelsus Medical University, Salzburg, Austria
* Equal contribution

Received: April 25, 2015       Accepted: May 30, 2015       Published: June 14, 2015
How to Cite

Copyright: © 2015 Breitenbach et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The aging process of skin has been investigated recently with respect to mitochondrial function and oxidative stress. We have here observed striking phenotypic and clinical similarity between skin aging and recessive dystrophic Epidermolysis bullosa (RDEB), which is caused by recessive mutations in the gene coding for collagen VII, COL7A1. Ultrastructural changes, defects in wound healing, and inflammation markers are in part shared with aged skin. We have here compared the skin transcriptomes of young adults suffering from RDEB with that of sex‐ and age‐matched healthy probands. In parallel we have compared the skin transcriptome of healthy young adults with that of elderly healthy donors. Quite surprisingly, there was a large overlap of the two gene lists that concerned a limited number of functional protein families. Most prominent among the proteins found are a number of proteins of the cornified envelope or proteins mechanistically involved in cornification and other skin proteins. Further, the overlap list contains a large number of genes with a known role in inflammation. We are documenting some of the most prominent ultrastructural and protein changes by immunofluorescence analysis of skin sections from patients, old individuals, and healthy controls.


RDEB: recessive dystrophic epidermolysis bullosa; EB: epidermolysis bullosa; CE: cornified envelope; PBS: phosphate buffered saline; TBS: TRIS buffered saline; PFA: para-formaldehyde; RT: room temperature; BSA: bovine serum albumin; RGB: + SPRR: small proline rich proteins; EDC: epidermal differentiation complex; LOR: loricrin; LCE: late cornified envelope; LCE1B: late cornified envelope protein 1B; RAGE: receptor for advanced glycation end products; ITGEB6: integrin beta 6; TGF-beta1: transforming growth factor beta 1; FLG: filaggrin; FLG2: filaggrin family member 2; LAMB4: laminin subunit beta 4; BL: basal lamina; CST6: cystatin E/M; KRT16: keratin 16; KRT6A: keratin 6A; KRT6B: keratin 6B; KRT2: keratin 2; KRT77: keratin77; IFNalpha: interferon alpha; IFNGR1: alpha subunit of interferon gamma receptor; IFI: group name of genes which are induced by interferon alpha; MDA5: melanoma differentiation associated gene 5; IL13RA1: alpha subunit of the receptor for interleukin 13; IL4R: alpha chain of the interleukin 4 receptor; IL8: interleukin 8; DEFB124: defensin beta 124; DEFB4: defensin beta 4; CXCL12: CXC chemokine ligand 12; CXCL13: CXC chemokine ligand 13; CCL2: CC chemokine ligand 2; CCL5: CC chemokine ligand 5; CFI: complement factor I; SCC: squamous cell carcinoma; CD47: cluster determinant 47 (a cell surface protein of the immune system); TNFRSF19: member 19 of the tumor necrosis factor receptor superfamily; MST1: macrophage stimulating factor 1; MSTP9: nuclear factor of activated T cells C2 IL1F7: interleukin 1 F7 (inhibitory member of the interleukin family); IL1R2: interleukin 1 receptor 2 (a soluble decoy receptor); IL22RA1: interleukin 22 receptor A1; IR: immunoreactivity.