Inhibition of Hsp90 Counteracts the Established Experimental Dermal Fibrosis Induced by Bleomycin
Identifikátory výsledku
Kód výsledku v 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>
Nalezeny alternativní kódy
RIV/00023728:_____/21:N0000039 RIV/00216208:11110/21:10429426
Výsledek na webu
<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>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Inhibition of Hsp90 Counteracts the Established Experimental Dermal Fibrosis Induced by Bleomycin
Popis výsledku v původním jazyce
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.
Název v anglickém jazyce
Inhibition of Hsp90 Counteracts the Established Experimental Dermal Fibrosis Induced by Bleomycin
Popis výsledku anglicky
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.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30226 - Rheumatology
Návaznosti výsledku
Projekt
<a href="/cs/project/NV16-33542A" target="_blank" >NV16-33542A: Role Hsp90 (Heat shock protein 90) u vybraných revmatických onemocnění</a><br>
Návaznosti
S - Specificky vyzkum na vysokych skolach
Ostatní
Rok uplatnění
2021
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Biomedicines [online]
ISSN
2227-9059
e-ISSN
—
Svazek periodika
9
Číslo periodika v rámci svazku
6
Stát vydavatele periodika
CH - Švýcarská konfederace
Počet stran výsledku
18
Strana od-do
650
Kód UT WoS článku
000667376600001
EID výsledku v databázi Scopus
2-s2.0-85108591653