Evidence map›Paper›PMID 34200311›Full record

ArticleBiomedicines2021

Inhibition of Hsp90 Counteracts the Established Experimental Dermal Fibrosis Induced by Bleomycin.

Hana Štorkánová, Lenka Štorkánová, Adéla Navrátilová, Viktor Bečvář, Hana Hulejová, Sabína Oreská, Barbora Heřmánková, Maja Špiritović, Radim Bečvář, Karel Pavelka and 4 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Biomedicines, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

6 citing papers in PubMed, 6 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 2 countries.

Hana ŠtorkánováInstitute of Rheumatology, 12800 Prague, Czech Republic.ORCID 0000-0002-6416-8385
Lenka ŠtorkánováInstitute of Rheumatology, 12800 Prague, Czech Republic.
Adéla NavrátilováInstitute of Rheumatology, 12800 Prague, Czech Republic.
Viktor BečvářInstitute of Rheumatology, 12800 Prague, Czech Republic.
Hana HulejováInstitute of Rheumatology, 12800 Prague, Czech Republic.
Sabína OreskáInstitute of Rheumatology, 12800 Prague, Czech Republic.
Barbora HeřmánkováDepartment of Physiotherapy, Faculty of Physical Education and Sport, Charles University, 16252 Prague, Czech Republic.
Maja ŠpiritovićInstitute of Rheumatology, 12800 Prague, Czech Republic.
Radim BečvářInstitute of Rheumatology, 12800 Prague, Czech Republic.
Karel PavelkaInstitute of Rheumatology, 12800 Prague, Czech Republic.
Jiří VencovskýInstitute of Rheumatology, 12800 Prague, Czech Republic.ORCID 0000-0002-0851-0713
Jörg H W DistlerDepartment of Internal Medicine III and Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
Ladislav ŠenoltInstitute of Rheumatology, 12800 Prague, Czech Republic.
Michal TomčíkInstitute of Rheumatology, 12800 Prague, Czech Republic.ORCID 0000-0002-8616-7850
Charles University · CZInstitute of Rheumatology · CZFriedrich-Alexander-Universität Erlangen-Nürnberg · DE

Funding

Ministerstvo Školství, Mládeže a Tělovýchovy SVV 260523Ministerstvo Zdravotnictví Ceské Republiky 00023728Ministerstvo Zdravotnictví Ceské Republiky 16-33542A
6 · The paper itself

Abstract

Our previous study demonstrated that heat shock protein 90 (Hsp90) is overexpressed in the involved skin of patients with systemic sclerosis (SSc) and in experimental dermal fibrosis. Pharmacological inhibition of Hsp90 prevented the stimulatory effects of transforming growth factor-beta on collagen synthesis and the development of dermal fibrosis in three preclinical models of SSc. In the next step of the preclinical analysis, herein, we aimed to evaluate the efficacy of an Hsp90 inhibitor, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), in the treatment of established experimental dermal fibrosis induced by bleomycin. Treatment with 17-DMAG demonstrated potent antifibrotic and anti-inflammatory properties: it decreased dermal thickening, collagen content, myofibroblast count, expression of transforming growth factor beta receptors, and pSmad3-positive cell counts, as well as leukocyte infiltration and systemic levels of crucial cytokines/chemokines involved in the pathogenesis of SSc, compared to vehicle-treated mice. 17-DMAG effectively prevented further progression and may induce regression of established bleomycin-induced dermal fibrosis to an extent comparable to nintedanib. These findings provide further evidence of the vital role of Hsp90 in the pathophysiology of SSc and characterize it as a potential target for the treatment of fibrosis with translational implications due to the availability of several Hsp90 inhibitors in clinical trials for other indications.

Indexed as

established dermal fibrosisheat shock protein 90systemic sclerosistreatment

Identifiers

PMID34200311
PMCPMC8226767
OpenAlexW3173015742

What Socratic 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 Socratic graph.