Whole-transcriptome gene expression profiling in an epidermolysis bullosa simplex Dowling-Meara model keratinocyte cell line uncovered novel, potential therapeutic targets and affected pathways

Herzog, Julia; Rid, Raphaela; Wagner, Martin; Hundsberger, Harald; Eger, Andreas; Bauer, Johann; Önder, Kamil
December 2015
BMC Research Notes;12/15/2015, Vol. 8, p1
Academic Journal
Background: To be able to develop effective therapeutics for epidermolysis bullosa simplex (EBS), it is necessary to elucidate the molecular pathomechanisms that give rise to the disease's characteristic severe skin-blistering phenotype. Results: Starting with a whole-transcriptome microarray analysis of an EBS Dowling-Meara model cell line (KEB7), we identified 207 genes showing differential expression relative to control keratinocytes. A complementary qRT-PCR study of 156 candidates confirmed 76.58 % of the selected genes to be significantly up-regulated or down-regulated (p-value <0.05) within biological replicates. Our hit list contains previously identified genes involved in epithelial cell proliferation, cell-substrate adhesion, and responses to diverse biological stimuli. In addition, we identified novel candidate genes and potential affected pathways not previously considered as relevant to EBS pathology. Conclusions: Our results broaden our understanding of the molecular processes dysregulated in EBS.


Related Articles

  • Genome-wide expression profiling and functional characterization of SCA28 lymphoblastoid cell lines reveal impairment in cell growth and activation of apoptotic pathways. Mancini, Cecilia; Roncaglia, Paola; Brussino, Alessandro; Stevanin, Giovanni; Lo Buono, Nicola; Krmac, Helena; Maltecca, Francesca; Gazzano, Elena; Stella, Anna Bartoletti; Calvaruso, Maria Antonietta; Iommarini, Luisa; Cagnoli, Claudia; Forlani, Sylvie; Le Ber, Isabelle; Durr, Alexandra; Brice, Alexis; Ghigo, Dario; Casari, Giorgio; Porcelli, Anna Maria; Funaro, Ada // BMC Medical Genomics;2013, Vol. 6 Issue 1, p1 

    Background: SCA28 is an autosomal dominant ataxia associated with AFG3L2 gene mutations. We performed a whole genome expression profiling using lymphoblastoid cell lines (LCLs) from four SCA28 patients and six unrelated healthy controls matched for sex and age. Methods: Gene expression was...

  • Identification of microRNAs specific for high producer CHO cell lines using steady-state cultivation. Maccani, Andreas; Hackl, Matthias; Leitner, Christian; Steinfellner, Willibald; Graf, Alexandra; Tatto, Nadine; Karbiener, Michael; Scheideler, Marcel; Grillari, Johannes; Mattanovich, Diethard; Kunert, Renate; Borth, Nicole; Grabherr, Reingard; Ernst, Wolfgang // Applied Microbiology & Biotechnology;Sep2014, Vol. 98 Issue 17, p7535 

    MicroRNAs are short non-coding RNAs that play an important role in the regulation of gene expression. Hence, microRNAs are considered as potential targets for engineering of Chinese hamster ovary (CHO) cells to improve recombinant protein production. Here, we analyzed and compared the microRNA...

  • Corrective gene transfer of keratinocytes from patients with junctional epidermolysis bullosa restores assembly of hemidesmosomes in reconstructed epithelia. Vailly, J; Gagnoux-Palacios, L; Dell’Ambra, E; Roméro, C; Pinola, M; Zambruno, G; De Luca, M; Ortonne, J-P; Meneguzzi, G // Gene Therapy;Oct98, Vol. 5 Issue 10, p1322 

    Herlitz junctional epidermolysis bullosa (H-JEB) provides a promising model for somatic gene therapy of heritable mechano-bullous disorders. This genodermatosis is caused by the lack of laminin-5 that results in absence of hemidesmosomes (HD) and defective adhesion of squamous epithelia. To...

  • A Homozygous Nonsense Mutation within the Dystonin Gene Coding for the Coiled-Coil Domain of the Epithelial Isoform of BPAG1 Underlies a New Subtype of Autosomal Recessive Epidermolysis Bullosa Simplex. Groves, Richard W.; Lu Liu; Dopping-Hepenstal, Patricia J.; Markus, Hugh S.; Lovell, Patricia A.; Ozoemena, Linda; Lai-Cheong, Joey E.; Gawler, Jeffrey; Owaribe, Katsushi; Hashimoto, Takashi; Mellerio, Jemima E.; Mee, John B.; McGrath, John A. // Journal of Investigative Dermatology;Jun2010, Vol. 130 Issue 6, p1551 

    Epidermolysis bullosa (EB) is a group of autosomal dominant and recessive blistering skin diseases in which pathogenic mutations have been reported in 13 different genes encoding structural proteins involved in keratinocyte integrity, as well as cell–matrix or cell–cell adhesion....

  • GATM locus does not replicate in rhabdomyolysis study. Floyd, James S.; Bis, Joshua C.; Brody, Jennifer A.; Heckbert, Susan R.; Rice, Kenneth; Psaty, Bruce M. // Nature;9/18/2014, Vol. 513 Issue 7518, pE1 

    Arising from L. M. Mangravite et al. 502, 377-380 (2013); doi:10.1038/nature12508All HMG-CoA reductase inhibitors (statins) can cause muscle injury ranging from asymptomatic elevations in creatine kinase levels to severe muscle breakdown (rhabdomyolysis) leading to kidney failure and death, and...

  • Keratinocyte-based cell assays: their potential pitfalls. Zupancic, Tina; Ozir, Mateja; Törmä, Hans; Komel, Radovan; Liovic, Mirjana // Archives of Dermatological Research;Nov2012, Vol. 304 Issue 9, p765 

    As an in vitro model system, patient-derived epidermolysis bullosa simplex keratinocytes have had an immense impact on what we know today about keratin filament function and their role in disease development. In the absence of gene therapy, screening compound libraries for new or better drugs is...

  • Nucleofection: A New Method for Cutaneous Gene Transfer? Jacobsen, Frank; Mertens-Rill, Janine; Beller, Juergen; Hirsch, Tobias; Daigeler, Adrien; Langer, Stefan; Lehnhardt, Marcus; Steinau, Hans-Ulrich; Steinstraesser, Lars // Journal of Biomedicine & Biotechnology;2006 Regular issue, p1 

    Background. Transfection efficacy after nonviral gene transfer in primary epithelial cells is limited. The aim of this study was to compare transfection efficacy of the recently available method of nucleofection with the established transfection reagent FuGENE6. Methods. Primary human...

  • Mammary Epithelial Cell Lineage Changes During Cow's Life. Finot, Laurence; Chanat, Eric; Dessauge, Frederic // Journal of Mammary Gland Biology & Neoplasia;Jun2019, Vol. 24 Issue 2, p185 

    Milk production is highly dependent on the optimal development of the mammary epithelium. It is therefore essential to better understand mammary epithelial cell growth and maintenance from the related epithelial lineage during the animal life. Here, we characterized the epithelial lineage at...

  • MMP-9 and CXCL8/IL-8 Are Potential Therapeutic Targets in Epidermolysis Bullosa Simplex. Lettner, Thomas; Lang, Roland; Klausegger, Alfred; Hainzl, Stefan; Bauer, Johann W.; Wally, Verena // PLoS ONE;Jul2013, Vol. 8 Issue 7, p1 

    Epidermolysis bullosa refers to a group of genodermatoses that affects the integrity of epithelial layers, phenotypically resulting in severe skin blistering. Dowling-Meara, the major subtype of epidermolysis bullosa simplex, is inherited in an autosomal dominant manner and can be caused by...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics