The serine proteases dipeptidyl-peptidase 4 and urokinase are key molecules in human and mouse scar formation

Vorstandlechner, Vera; Laggner, Maria; Copic, Dragan; Klas, Katharina; Direder, Martin; Chen, Yiyan; Golabi, Bahar; Haslik, Werner; Radtke, Christine; Tschachler, Erwin; Hötzenecker, Konrad; Ankersmit, Hendrik Jan; Mildner, Michael

doi:10.1038/s41467-021-26495-2

Cited by 52 publications

(58 citation statements)

References 79 publications

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“…To date, several studies have underlined the impact of the tissue dissociation procedure on gene expression [37][38][39] . The commercially available whole-skin dissociation kit is the most commonly used skin dissociation method for scRNA-seq experiments 22,42 and was used in 3 of the 4 studies analyzed (Supplementary Table 7). In only one study, keloids were digested with dispase II and collagenase IV for two hours.…”

Section: Discussionmentioning

confidence: 99%

The transcriptional profile of keloidal Schwann cells

et al. 2022

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Recently, a specific Schwann cell type with profibrotic and tissue regenerative properties that contributes to keloid formation has been identified. In the present study, we reanalyzed published single-cell RNA sequencing (scRNA-seq) studies of keloids, healthy skin, and normal scars to reliably determine the specific gene expression profile of keloid-specific Schwann cell types in more detail. We were able to confirm the presence of the repair-like, profibrotic Schwann cell type in the datasets of all three studies and identified a specific gene-set for these Schwann cells. In contrast to keloids, in normal scars, the number of Schwann cells was not increased, nor was their gene expression profile distinctly different from that of Schwann cells of normal skin. In addition, our bioinformatics analysis provided evidence for a role of transcription factors of the AP1, STAT, and KLF families, and members of the IER genes in the dedifferentiation process of keloidal Schwann cells. Together, our analysis strengthens the role of the profibrotic Schwann cell type in the formation of keloids. Knowledge of the exact gene expression profile of these Schwann cells will facilitate their identification in other organs and diseases.

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Section: Discussionmentioning

confidence: 99%

The transcriptional profile of keloidal Schwann cells

et al. 2022

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“…TGF- β pathway controls a wide variety of cellular processes, ranging from cell proliferation and differentiation to tissue homeostasis and regeneration via SMAD-dependent (canonical) and independent (noncanonical) signaling [ 57 , 58 ]. Based on functional analysis, boosted myofibroblast differentiation and excessive deposition of ECM have been observed due to increased levels of TGF- β 1, mediated by Dpp4 and urokinase (PLAU) in vitro [ 59 ].…”

Section: Regulation Of Fibroblasts In Wound Healing and Scar Formationmentioning

confidence: 99%

Fibroblasts in Scar Formation: Biology and Clinical Translation

Qian

Shan

Gong

et al. 2022

Oxidative Medicine and Cellular Longevity

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Scarring, which develops due to fibroblast activation and excessive extracellular matrix deposition, can cause physical, psychological, and cosmetic problems. Fibroblasts are the main type of connective tissue cells and play important roles in wound healing. However, the underlying mechanisms of fibroblast in reaching scarless wound healing require more exploration. Herein, we systematically reviewed how fibroblasts behave in response to skin injuries, as well as their functions in regeneration and scar formation. Several biocompatible materials, including hydrogels and nanoparticles, were also suggested. Moreover, factors that concern transformation from fibroblasts into cancer-associated fibroblasts are mentioned due to a tight association between scar formation and primary skin cancers. These findings will help us better understand skin fibrotic pathogenesis, as well as provide potential targets for scarless wound healing therapies.

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“…So far, several studies have underlined the impact of the tissue dissociation procedure on gene expression 50-52 . The commercially available whole skin dissociation kit is the most commonly used skin dissociation method for scRNAseq experiments 36,55 , and was used in 3 of 4 studies analysed (Table 2). Only in one study, keloids were digested with dispase II and collagenase IV for two hours.…”

Section: Discussionmentioning

confidence: 99%

The transcriptional profile of keloidal Schwann cells

Direder

Wielscher

Weiss

et al. 2022

Preprint

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Recently, a specific Schwann cell type with pro-fibrotic and tissue regenerative properties has been identified that contributes to keloid formation. In the present study, we have re-analysed published single cell RNA sequencing (scRNAseq) studies of keloids, healthy skin and normal scars to reliably determine the specific gene expression profile of the keloid-specific Schwann cell type in more detail. We were able to confirm the presence of the repair-like, pro-fibrotic Schwann cell type in the datasets of all three studies and identified a specific gene set for these Schwann cells. In contrast to keloids, in normal scars the number of Schwann cells was neither increased nor was their gene expression profile distinctly different from Schwann cells of normal skin. In addition, our bioinformatics analysis provided evidence for a role of transcription factors of the kruppel-like factor family and members of the immediate early response genes, in the de-differentiation process of keloidal Schwann cells. Together, our analysis strengthens the role of the pro-fibrotic Schwann cell type in the formation of keloids. Knowledge on the exact gene expression profile of these Schwann cells will facilitate their identification in other organs and diseases.

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The serine proteases dipeptidyl-peptidase 4 and urokinase are key molecules in human and mouse scar formation

Cited by 52 publications

References 79 publications

The transcriptional profile of keloidal Schwann cells

The transcriptional profile of keloidal Schwann cells

Fibroblasts in Scar Formation: Biology and Clinical Translation

The transcriptional profile of keloidal Schwann cells

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