Original Article
Wound Healing
Proteomic Profiling of Fibroblasts Isolated from Chronic Wounds Identifies Disease-Relevant Signaling Pathways

https://doi.org/10.1016/j.jid.2020.02.040Get rights and content
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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.

Abbreviations

5-aza
5-azacytidine
aWAF
acute wound–associated fibroblast
cWAF
chronic wound–associated fibroblast
ECM
extracellular matrix
MS
mass spectrometry
NHF
normal human fibroblast
ruxo
ruxolitinib

Cited by (0)

4

These authors contributed equally to this work.

5

These authors contributed equally to this work.