The serine proteases dipeptidyl-peptidase 4 and urokinase are key molecules in human and mouse scar formation
Updated November 7, 2023Despite recent advances in understanding skin scarring, mechanisms triggering hypertrophic scar formation are still poorly understood. In the present study, we investigate mature human hypertrophic scars and developing scars in mice at single cell resolution. Compared to normal skin, we find significant differences in gene expression in most cell types present in scar tissue. Fibroblasts show the most prominent alterations in gene expression, displaying a distinct fibrotic signature. By comparing genes upregulated in murine fibroblasts during scar development with genes highly expressed in mature human hypertrophic scars, we identify a group of serine proteases, tentatively involved in scar formation. Two of them, dipeptidyl-peptidase 4 (DPP4) and urokinase (PLAU), are further analyzed in functional assays, revealing a role in TGFβ1-mediated myofibroblast differentiation and over-production of components of the extracellular matrix in vitro. Topical treatment with inhibitors of DPP4 and PLAU during scar formation in vivo shows anti-fibrotic activity and improvement of scar quality, most prominently after application of the PLAU inhibitor BC-11. In this study, we delineate the genetic landscape of hypertrophic scars and present insights into mechanisms involved in hypertrophic scar formation. Our data suggest the use of serine protease inhibitors for the treatment of skin fibrosis.
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Analysis Portals
NoneProject Label
skin-serine-proteasesSpecies
Sample Type
Anatomical Entity
Organ Part
Selected Cell Types
Disease Status (Specimen)
Disease Status (Donor)
Development Stage
Library Construction Method
Nucleic Acid Source
Paired End
falseAnalysis Protocol
human_gex, mouse_gexFile Format
Cell Count Estimate
31.6kDonor Count
13