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

doi:10.1016/j.jid.2020.02.040

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

Berberich, Bettina Department of Dermatology, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg im Breisgau, Germany -
Thriene, Kerstin Department of Dermatology, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg im Breisgau, Germany - Institute for Prevention and Cancer Epidemiology, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg im Breisgau, Germany -
Gretzmeier, Christine Department of Dermatology, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg im Breisgau, Germany
Kühl, Tobias Department of Dermatology, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg im Breisgau, Germany
Bayer, Hans Department of Dermatology, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg im Breisgau, Germany
Athanasiou, Ioannis Department of Dermatology, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg im Breisgau, Germany
Rafei-Shamsabadi, David Ali Department of Dermatology, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg im Breisgau, Germany
Bruckner-Tuderman, Leena Department of Dermatology, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg im Breisgau, Germany
Nyström, Alexander Department of Dermatology, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg im Breisgau, Germany -
Kiritsi, Dimitra Department of Dermatology, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg im Breisgau, Germany -
Dengjel, Jörn Department of Biology, University of Fribourg, Fribourg, Switzerland

01.11.2020

Published in:

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

English 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 wounds, propagated them in vitro, and analyzed them using proteomic profiling in combination with functional characterization of the proteomic changes. Chronic wound–associated fibroblasts exhibit a unique proteome profile characteristic of lysosomal dysfunction and dysregulated TGFβ signaling. They display a decreased propensity for cell proliferation and migration, combined with an enhanced ability to contract the extracellular matrix. With these properties, chronic wound–associated fibroblasts actively contribute to pathological inabilities to close wounds and represent potential targets for pharmacological interference for changing cellular phenotypes.

Faculty

Faculté des sciences et de médecine

Department

Département de Biologie

Language