Evidence map›Paper›PMID 33228813›Full record

ArticleEuropean journal of medical research2020

Dose- and time-dependent effects of hyaluronidase on structural cells and the extracellular matrix of the skin.

Bettina Alexandra Buhren, Holger Schrumpf, Katharina Gorges, Oliver Reiners, Edwin Bölke, Jens W Fischer, Bernhard Homey, Peter Arne Gerber

Open access · goldAbstract read
In one paragraph

Article in European journal of medical research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

  1. A Systematic Review of Keratinocyte Secretions: A Regenerative Perspective.International journal of molecular sciences · 2022
    Pooled it
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  6. Comprehensive Evaluation ofPlants (Basel, Switzerland) · 2025
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  9. A Tensioned Human Skin Explant Model Used for Preliminary Assessment of Chemexfoliant-Stimulated Bioeffects.JID innovations : skin science from molecules to population health · 2025
    Article
  10. Article
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  12. Review
  13. Article
  14. Article
  15. Article
  16. Kahweol Exerts Skin Moisturizing Activities by Upregulating STAT1 Activity.International journal of molecular sciences · 2021
    Article
  17. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Bettina Alexandra BuhrenDepartment of Dermatology, University Hospital Duesseldorf, Duesseldorf, Germany.
Holger SchrumpfDepartment of Dermatology, University Hospital Duesseldorf, Duesseldorf, Germany.
Katharina GorgesDepartment of Pharmacology, University Hospital Duesseldorf, Duesseldorf, Germany.
Oliver ReinersDepartment of Pharmacology, University Hospital Duesseldorf, Duesseldorf, Germany.
Edwin BölkeDepartment of Radiation Oncology, Medical Faculty, University Hospital Duesseldorf, Duesseldorf, Germany.ORCID http://orcid.org/0000-0001-9112-1024
Jens W FischerDepartment of Pharmacology, University Hospital Duesseldorf, Duesseldorf, Germany.
Bernhard HomeyDepartment of Dermatology, University Hospital Duesseldorf, Duesseldorf, Germany.
Peter Arne GerberDepartment of Dermatology, University Hospital Duesseldorf, Duesseldorf, Germany. prof.gerber@dermatologie-am-luegplatz.de.
Düsseldorf University Hospital · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionHyaluronic acid (hyaluronan; HA) is an essential component of the extracellular matrix (ECM) of the skin. The HA-degrading enzyme hyaluronidase (HYAL) is critically involved in the HA-metabolism. Yet, only little information is available regarding the skin's HA-HYAL interactions on the molecular and cellular levels.

objectiveTo analyze the dose- and time-dependent molecular and cellular effects of HYAL on structural cells and the HA-metabolism in the skin. MATERIALS AND

methodsChip-based, genome-wide expression analyses (Affymetrix® GeneChip PrimeView™ Human Gene Expression Array), quantitative real-time PCR analyses, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (DAB), and in vitro wound healing assays were performed to assess dose-dependent and time-kinetic effects of HA and HYAL (bovine hyaluronidase, Hylase "Dessau") on normal human dermal fibroblasts (NHDF), primary human keratinocytes in vitro and human skin samples ex vivo.

resultsGenome-wide expression analyses revealed an upregulation of HA synthases (HAS) up to 1.8-fold change in HA- and HYAL-treated NHDF. HA and HYAL significantly accelerated wound closure in an in vitro model for cutaneous wound healing. HYAL induced HAS1 and HAS2 mRNA gene expression in NHDF. Interestingly, low concentrations of HYAL (0.015 U/ml) resulted in a significantly higher induction of HAS compared to moderate (0.15 and 1.5 U/ml) and high concentrations (15 U/ml) of HYAL. This observation corresponded to increased concentrations of HA measured by ELISA in conditioned supernatants of HYAL-treated NHDF with the highest concentrations observed for 0.015 U/ml of HYAL. Finally, immunohistochemical analysis of human skin samples incubated with HYAL for up to 48 h ex vivo demonstrated that low concentrations of HYAL (0.015 U/ml) led to a pronounced accumulation of HA, whereas high concentrations of HYAL (15 U/ml) reduced dermal HA-levels.

conclusionHYAL is a bioactive enzyme that exerts multiple effects on the HA-metabolism as well as on the structural cells of the skin. Our results indicate that HYAL promotes wound healing and exerts a dose-dependent induction of HA-synthesis in structural cells of the skin. Herein, interestingly the most significant induction of HAS and HA were observed for the lowest concentration of HYAL.

Indexed as

AnimalsCattleCells, CulturedDose-Response Relationship, DrugExtracellular MatrixFibroblastsGene ExpressionHumansHyaluronan SynthasesHyaluronic AcidHyaluronoglucosaminidaseKeratinocytesSkinTime FactorsWound HealingHyaluronan SynthasesHyaluronic AcidHyaluronoglucosaminidaseCellDermatologyEnzymesMetabolismSkin

Identifiers

PMID33228813
PMCPMC7686775
OpenAlexW3103712630

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.