Dataset Information

Human cWAF LC-MS/MS

ABSTRACT: Chronic skin wounds accompany many widespread, chronic and age-related diseases and are a major cause of morbidity and mortality. Both, keratinocytes and skin fibroblasts contribute to the pathomechanisms observed in chronic wounds. Whereas dysregulated pathways in the epidermis have been extensively studied, little is known on the influence of dermal fibroblasts on chronic wounding. We isolated fibroblasts from chronic wounds and show that they are a distinct cell type that can be propagated in vitro. Chronic wound-associated fibroblasts (cWAFs) exhibit a unique proteome profile characteristic for a decreased propensity for cell proliferation and migration but with an enhanced ability to contract the extracellular matrix. Commonly, they display lysosomal dysfunction and dysregulated TGFbeta signaling. Here, we define intrinsic and extrinsic properties of cWAFs that may contribute to pathological wound healing.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Skin, Fibroblast

DISEASE(S): Wounds And Injuries

SUBMITTER: Joern Dengjel

LAB HEAD: Joern Dengjel

PROVIDER: PXD007704 | Pride | 2020-10-29

REPOSITORIES: Pride

ACCESS DATA

Publications

Proteomic Profiling of Fibroblasts Isolated from Chronic Wounds Identifies Disease-Relevant Signaling Pathways.

Berberich Bettina B Thriene Kerstin K Gretzmeier Christine C Kühl Tobias T Bayer Hans H Athanasiou Ioannis I Rafei-Shamsabadi David Ali DA Bruckner-Tuderman Leena L Nyström Alexander A Kiritsi Dimitra D Dengjel Jörn J

The Journal of investigative dermatology 20200417 11

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 functi ...[more]

PMID: 32305317

Similar Datasets

Project description:In adult mammals, skin wound healing has evolved to favor rapid repair through formation of fibrotic scar. Consequently, skin wounds are dysfunctional and lead to chronic disfigurement and disability, yet the biologic mechanisms that drive fibrosis and prevent tissue regeneration remain unknown. Here, we report that reindeer (Rangifer tarandus) antler velvet exhibits regenerative wound healing, whereas identical full-thickness injury in dorsal back skin forms fibrotic scar. This regenerative capacity is retained even following ectopic transplantation of velvet to a scar-forming site, demonstrating that this latent regenerative capacity is innate to velvet cells and independent of local factors derived from the growing antler. Single cell RNA-sequencing of uninjured skin revealed a marked divergence in resting fibroblast transcriptional states and immunomodulatory function. Uninjured velvet fibroblast shared a striking resemblance with human fetal fibroblasts whereas uninjured back skin fibroblasts exhibited an overrepresentation of pro-inflammatory genes resembling adult human fibroblasts. Identical skin injury resulted in site-specific fibroblast polarization; back fibroblasts exacerbated the inflammatory response, whereas velvet fibroblasts adopted an immunosuppressive state and reverted back to a regeneration-competent ground state. Consequently, velvet wounds exhibited reduced immune infiltrate, accelerated adoption of anti-inflammatory immune states and expedited resolution of immune response. This study demonstrates reindeer as a novel mammalian model to study adult skin regeneration (velvet) and scar formation (back skin) within the same animal. Our study underscores the importance of fibroblast heterogeneity in shaping local immune cell functions that ultimately polarize wound healing outcomes. Purposeful, acute modulation of fibroblast-mediated immune signaling represents an important therapeutic avenue to mitigate scar and improve wound healing.

Dataset Information

Human cWAF LC-MS/MS

Publications

Proteomic Profiling of Fibroblasts Isolated from Chronic Wounds Identifies Disease-Relevant Signaling Pathways.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure