Hajimiragha H

Krutmann J

Majora M

Schroeder P

Schuermann BA

BA Schuermann

M Majora

P Schroeder

H Hajimiragha

J Krutmann

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Cell Communication and Signaling
Open AccessMeeting abstract
Increased levels of large scale deletions of mtDNA of skin fibroblasts 
result in increased collagen degradation in dermal skin equivalents
BA Schuermann*, M Majora, P Schroeder, H Hajimiragha and J Krutmann
Address: IUF, Molekulare Alternsforschung, Duesseldorf, Germany
* Corresponding author    
Aged tissues contain increased levels of large-scale dele-
tions of the mitochondrial (mt) DNA. Especially extrinsi-
cally aged skin has been shown to carry a significant
burden of mtDNA deletions along with several other
structural and functional impairments. Until now the
functional role of mtDNA mutations for functional and
structural changes of aged skin is not understood.
Therefore we studied how human skin cells harbouring
mtDNA mutations affect their microenvironment by com-
paring normal human fibroblasts (NHF) to dermal
fibroblasts derived from patients suffering from Kearns-
Sayre syndrome (KSS) in 3D collagen gels resembling
human skin (dermal equivalents, DE). KSS fibroblasts
carry a 10,000 fold higher amount of mtDNA deletions
exemplified by quantitative measurement of the 4977 bp
Common Deletion. We here examined the degradation of
components of the extracellular matrix in DE during cul-
tivation.
During six weeks we detected more fragmented collagen
measured by the marker hydroxyproline (HYP) via GC-
MS. Moreover we observed a less robust collagen lattice
structure in dermal equivalents with KSS fibroblasts in
comparison to NHF by picrosirius red staining of histo-
logical sections. In line with that, we could measure
higher mRNA expression levels of the dominant collagen
degrading enzyme matrixmetalloproteinase-1 (MMP-1)
in KSS DE using realtime PCR and increased MMP-1 pro-
tein amounts in histological sections over the whole culti-
vation time.
We conclude that increased levels of photo-inducible
mtDNA deletions are functionally relevant for intensified
matrix degradation and are therefore responsible for det-
rimental changes in photoaged skin.
from 12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes
Weimar, Germany. 29–31 October 2008
Published: 26 February 2009
Cell Communication and Signaling 2009, 7(Suppl 1):A67 doi:10.1186/1478-811X-7-S1-A67
<supplement> <title> <p>12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes</p> </title> <editor>Frank Entschladen, Karlheinz Friedrich, Ralf Hass and Ottmar Janssen</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1478-811X-7-S1-full.pdf">here</a>.</note> </supplement>
This abstract is available from: http://www.biosignaling.com/content/7/S1/A67
© 2009 Schuermann et al; licensee BioMed Central Ltd. 


Increased levels of large scale deletions of mtDNA of skin fibroblasts result in increased collagen degradation in dermal skin equivalents

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Increased levels of large scale deletions of mtDNA of skin fibroblasts result in increased collagen degradation in dermal skin equivalents

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