ArticleNature communications2021
The serine proteases dipeptidyl-peptidase 4 and urokinase are key molecules in human and mouse scar formation.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Fibroblasts in Scar Formation: Biology and Clinical Translation.Oxidative medicine and cellular longevity · 2022Pooled it
- [Effect of different degrees of wound eversion sutures on scar formation at donor site of anterolateral thigh flaps: A prospective randomized controlled study].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2024Trial
- Resveratrol Ameliorates Hypertrophic Scar Formation by Regulating ASIC3-Mediated Fibroblast-Macrophage Crosstalk: A Mechanistic Study.Phytotherapy research : PTR · 2026Article
- Association of DPP4 with esophageal stricture progression and the Hippo-YAP pathway.Animal models and experimental medicine · 2026Article
- Anti-fibrotic effects of evogliptin in fibroblasts derived from post-burn hypertrophic scars.Scientific reports · 2026Article
- Rational design of FAP-targeted sEVs delivered by microneedles for precision treatment of hypertrophic scars via ferroptosis in hypertrophic scar fibroblasts.Materials today. Bio · 2026Article
- Deep phenotyping of skin tissue remodeling in patients with systemic sclerosis treated with CD19-CAR T cells.Nature communications · 2026Article
- Single-Cell Analysis of Fibroblast Subpopulations in Skin and Oral Mucosa.Journal of dental research · 2026Review
- Single-cell spatial transcriptomic analysis of human skin anatomy.Nature genetics · 2026Article
- Approaching Scarless Wound Healing: From Passive Anti-Fibrotic to Proactive and Programmable Pro-Regenerative Strategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Targeting NRP1 in Endothelial Cells Facilitates the Normalization of Scar Vessels and Prevents Fibrotic Scarring.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Burn Selection: How Fire Injury Shaped Human Evolution.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Baicalein inhibits the progression of thyroid cancer by suppressing the TPL2/MEK2/ERK2 pathway.Frontiers in endocrinology · 2026Article
- Single-cell transcriptomic profiling identifies YY1 as a key regulator of fibroblast plasticity in hypertrophic scar formation.Burns & trauma · 2026Article
- Deciphering the cellular landscape of pathological scars.Burns & trauma · 2026Article
- Spatiotemporal decoding of skin biology: development, aging, disease, and regeneration.Burns & trauma · 2026Article
- Immune-dominated cellular heterogeneity and stromal plasticity in keloid infiltrating and hypercellular zones revealed by single-cell RNA sequencing.Frontiers in immunology · 2026Article
- PLAU promotes fibroblast activation and keloid fibrogenesis through PLAUR-Dependent TGF-β/Smad signaling.Frontiers in immunology · 2026Article
- RestoringFrontiers in cell and developmental biology · 2026Article
- Modulating hypertrophic scar formation by targeting endothelial transient receptor potential vanilloid-1/nuclear factor kappa-B/interleukin-6 axis to regulate angiogenesis.Burns & trauma · 2026Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite 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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.