Inhibition of Hsp90 Counteracts the Established Experimental Dermal Fibrosis Induced by Bleomycin
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11510%2F21%3A10429426" target="_blank" >RIV/00216208:11510/21:10429426 - isvavai.cz</a>
Alternative codes found
RIV/00023728:_____/21:N0000039 RIV/00216208:11110/21:10429426
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=xREDSw0SUK" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=xREDSw0SUK</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/biomedicines9060650" target="_blank" >10.3390/biomedicines9060650</a>
Alternative languages
Result language
angličtina
Original language name
Inhibition of Hsp90 Counteracts the Established Experimental Dermal Fibrosis Induced by Bleomycin
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30226 - Rheumatology
Result continuities
Project
<a href="/en/project/NV16-33542A" target="_blank" >NV16-33542A: The role of Hsp90 (Heat shock protein 90) in selected rheumatic diseases</a><br>
Continuities
S - Specificky vyzkum na vysokych skolach
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biomedicines [online]
ISSN
2227-9059
e-ISSN
—
Volume of the periodical
9
Issue of the periodical within the volume
6
Country of publishing house
CH - SWITZERLAND
Number of pages
18
Pages from-to
650
UT code for WoS article
000667376600001
EID of the result in the Scopus database
2-s2.0-85108591653