Naslov
Overactivation of Notch signaling in activated hepatic stellate cells does not lead to greater liver fibrosis nor does it inhibit its resolution
(Overactivation of Notch signaling in activated hepatic stellate cells does not lead to greater liver fibrosis nor does it inhibit its resolution)

Autori
Šisl, Dino ; Filipović, Maša ; Flegar, Darja ; Šućur, Alan ; Kovačić, Nataša ; Grčević, Danka ; Kelava, Tomislav

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Shaping the Future of Immunology in Europe, European Journal of Immunology 52(Suppl. 2) / - , 2022, 77-77

Skup
YEFIS 1st Symposium

Mjesto i datum
Berlin, Njemačka, 10.11.2022. - 11.11.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
liver fibrosis, Notch signaling pathway, mouse model, gene expression, hepatic stellate cells

Sažetak
Activated hepatic stellate cells (aHSCs) are a major source of myofibroblasts and modulating their signaling pathways may affect fibrogenesis. Recent findings suggested involvement of Notch signaling pathway in pathogenesis of liver fibrosis. We aimed to characterize the role of Notch overactivation in aHSCs in the development and resolution of liver fibrosis. SMACreERT/NICD (with Cre- littermates as control) mice were given CCl4 (0.5 mL/kg i.p., 2x weekly) for 6 weeks or were fed 0.025%-DDC- supplemented diet for 4 weeks. Tamoxifen was injected twice weekly (75 μg/kg i.p.) in order to activate the Cre recombinase in aHSCs. In the second set of experiments, mice were allowed a recovery period of 4 weeks following the 2 weeks of fibrosis induction. Liver tissue and sera were taken for analysis. ALT and AST activities were not significantly different between groups, and neither was gene expression of Col1a1 and Acta2. Percentage of sirius red stained area, calculated with ImageJ, did not differ between groups. This finding was confirmed by liver tissue hydroxyproline content, which was similar in both groups. Similar results were found in the recovery set of experiments, with no significant difference between groups biochemically (ALT, AST, hydroxyproline), histologically (red area percentage) nor on gene expression (Col1a1, Acta2). Overexpression of Notch1 in activated HSCs does not lead to greater fibrosis, nor does it inhibit its resolution upon removal of CCl4 or DDC.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA