Université de Fribourg

Skin proteomics – analysis of the extracellular matrix in health and disease

Dengjel, Jörn ; Bruckner-Tuderman, Leena ; Nyström, Alexander

In: Expert Review of Proteomics, 2020, vol. 17, no. 5, p. 377–391

Introduction The skin protects the human body from external insults and regulates water and temperature homeostasis. A highly developed extracellular matrix (ECM) supports the skin and instructs its cell functions. Reduced functionality of the ECM is often associated with skin diseases that cause physical impairment and also have implications on social interactions and quality of life of...

Université de Fribourg

Proteomic profiling of fibroblasts isolated from chronic wounds identifies disease-relevant signaling pathways

Berberich, Bettina ; Thriene, Kerstin ; Gretzmeier, Christine ; Kühl, Tobias ; Bayer, Hans ; Athanasiou, Ioannis ; Rafei-Shamsabadi, David Ali ; Bruckner-Tuderman, Leena ; Nyström, Alexander ; Kiritsi, Dimitra ; Dengjel, Jörn

In: Journal of Investigative Dermatology, 2020, vol. 140, no. 11, p. 2280-2290.e4

Chronic skin wounds accompany many prevalent age-related diseases and are a major cause of morbidity and mortality. Both keratinocytes and fibroblasts contribute to the pathomechanisms in chronic skin wounds. Dysregulated pathways in the epidermis have been extensively studied, but little is known of the influence of dermal fibroblasts on chronic wounding. We isolated fibroblasts from chronic...

Université de Fribourg

The Pseudomonas aeruginosa lectin LecB causes integrin internalization and inhibits epithelial wound healing

Thuenauer, Roland ; Landi, Alessia ; Trefzer, Anne ; Altmann, Silke ; Wehrum, Sarah ; Eierhoff, Thorsten ; Diedrich, Britta ; Dengjel, Jörn ; Nyström, Alexander ; Imberty, Anne ; Römer, Winfried

In: mBio, 2020, vol. 11, no. 2, p. -

The opportunistic bacterium Pseudomonas aeruginosa produces the fucose- specific lectin LecB, which has been identified as a virulence factor. LecB has a tetrameric structure with four opposing binding sites and has been shown to act as a cross-linker. Here, we demonstrate that LecB strongly binds to the glycosylated moieties of β1-integrins on the basolateral plasma membrane of epithelial...

Université de Fribourg

Treatment of keratinocytes with 4-phenylbutyrate in epidermolysis bullosa: Lessons for therapies in keratin disorders

Spörrer, Marina ; Prochnicki, Ania ; C.Tölle, Regine ; Nyström, Alexander ; Esser, Philipp R. ; Homberg, Melanie ; Athanasiou, Ioannis ; Zingkou, Eleni ; Schillinga, Achim ; Gerum, Richard ; Thievessen, Ingo ; Winter, Lilli ; Bruckner-Tuderman, Leena ; Fabry, Ben ; Magin, Thomas M. ; Dengjel, Jörn ; Schröder, Rolf ; Kiritsi, Dimitra

In: EBioMedicine, 2019, vol. 44, p. 502–515

Missense mutations in keratin 5 and 14 genes cause the severe skin fragility disorder epidermolysis bullosa simplex (EBS) by collapsing of the keratin cytoskeleton into cytoplasmic protein aggregates. Despite intense efforts, no molecular therapies are available, mostly due to the complex phenotype of EBS, comprising cell fragility, diminished adhesion, skin inflammation and itch.Methods: We...

Université de Fribourg

Impaired lymphoid extracellular matrix impedes antibacterial immunity in epidermolysis bullosa

Nyström, Alexander ; Bornert, Olivier ; Kühl, Tobias ; Gretzmeier, Christine ; Thriene, Kerstin ; Dengjel, Jörn ; Pfister-Wartha, Andrea ; Kiritsi, Dimitra ; Bruckner-Tuderman, Leena

In: Proceedings of the National Academy of Sciences, 2018, vol. 115, no. 4, p. E705–E714

Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB), a skin fragility disorder that, unexpectedly, manifests also with elevated colonization of commensal bacteria and frequent wound infections. Here, we describe an unprecedented systemic function of collagen VII as a member of a unique innate immune-supporting multiprotein complex in spleen and lymph nodes....

Université de Fribourg

Combinatorial omics analysis reveals perturbed lysosomal homeostasis in collagen VII-deficient keratinocytes

Thriene, Kerstin ; Grüning, Björn Andreas ; Bornert, Olivier ; Erxleben, Anika ; Leppert, Juna ; Athanasiou, Ioannis ; Weber, Ekkehard ; Kiritsi, Dimitra ; Nyström, Alexander ; Reinheckel, Thomas ; Backofen, Rolf ; Has, Cristina ; Bruckner-Tuderman, Leena ; Dengjel, Jörn

In: Molecular & Cellular Proteomics, 2018, vol. 17, no. 4, p. 565-579

The extracellular matrix protein collagen VII is part of the microenvironment of stratified epithelia and critical in organismal homeostasis. Mutations in the encoding gene COL7A1 lead to the skin disorder dystrophic epidermolysis bullosa (DEB), are linked to skin fragility and progressive inflammation-driven fibrosis that facilitates aggressive skin cancer. So far, these changes have been...