Pulling the Rug Out from Under: Biomechanical Microenvironment Remodeling for Induction of Hepatic Stellate Cell Quiescence

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62156489%3A43210%2F24%3A43925830" target="_blank" >RIV/62156489:43210/24:43925830 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1002/adma.202406590" target="_blank" >https://doi.org/10.1002/adma.202406590</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/adma.202406590" target="_blank" >10.1002/adma.202406590</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Pulling the Rug Out from Under: Biomechanical Microenvironment Remodeling for Induction of Hepatic Stellate Cell Quiescence

Popis výsledku v původním jazyce

Hepatic fibrosis progresses concomitantly with a variety of biomechanical alternations, especially increased liver stiffness. These biomechanical alterations have long been considered as pathological consequences. Recently, growing evidence proposes that these alternations result in the fibrotic biomechanical microenvironment, which drives the activation of hepatic stellate cells (HSCs). Here, an inorganic ascorbic acid-oxidase (AAO) mimicking nanozyme loaded with liquiritigenin (LQ) is developed to trigger remodeling of the fibrotic biomechanical microenvironment. The AAO mimicking nanozyme is able to consume intracellular ascorbic acid, thereby impeding collagen I deposition by reducing its availability. Simultaneously, LQ inhibits the transcription of lysyl oxidase like 2 (LOXL2), thus impeding collagen I crosslinking. Through its synergistic activities, the prepared nanosystem efficiently restores the fibrotic biomechanical microenvironment to a near-normal physiological condition, promoting the quiescence of HSCs and regression of fibrosis. This strategy of remodeling the fibrotic biomechanical microenvironment, akin to &quot;pulling the rug out from under&quot;, effectively treats hepatic fibrosis in mice, thereby highlighting the importance of tissue biomechanics and providing a potential approach to improve hepatic fibrosis treatment.

Název v anglickém jazyce

Pulling the Rug Out from Under: Biomechanical Microenvironment Remodeling for Induction of Hepatic Stellate Cell Quiescence

Popis výsledku anglicky

Hepatic fibrosis progresses concomitantly with a variety of biomechanical alternations, especially increased liver stiffness. These biomechanical alterations have long been considered as pathological consequences. Recently, growing evidence proposes that these alternations result in the fibrotic biomechanical microenvironment, which drives the activation of hepatic stellate cells (HSCs). Here, an inorganic ascorbic acid-oxidase (AAO) mimicking nanozyme loaded with liquiritigenin (LQ) is developed to trigger remodeling of the fibrotic biomechanical microenvironment. The AAO mimicking nanozyme is able to consume intracellular ascorbic acid, thereby impeding collagen I deposition by reducing its availability. Simultaneously, LQ inhibits the transcription of lysyl oxidase like 2 (LOXL2), thus impeding collagen I crosslinking. Through its synergistic activities, the prepared nanosystem efficiently restores the fibrotic biomechanical microenvironment to a near-normal physiological condition, promoting the quiescence of HSCs and regression of fibrosis. This strategy of remodeling the fibrotic biomechanical microenvironment, akin to &quot;pulling the rug out from under&quot;, effectively treats hepatic fibrosis in mice, thereby highlighting the importance of tissue biomechanics and providing a potential approach to improve hepatic fibrosis treatment.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GM23-04740M" target="_blank" >GM23-04740M: Hybridní biokompatibilní nanokatalyzátory pro extracelulární bioorthogonální aktivaci proléčiv</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Advanced Materials

ISSN

0935-9648

e-ISSN

1521-4095

Svazek periodika

36

Číslo periodika v rámci svazku

49

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

17

Strana od-do

2406590

Kód UT WoS článku

001331722700001

EID výsledku v databázi Scopus

2-s2.0-85206376170