Naslov
What is the role of canonical Notch signalling pathway in liver fibrosis?

Autori
Šisl, Dino ; Novak, Sanja ; Kalajzić, Ivo ; Filipović, Maša ; Flegar, Darja ; Šućur, Alan ; Kovačić, Nataša ; Grčević, Danka ; Markotić, Antonio ; Kelava, Tomislav

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

Izvornik
Annual meeting of the Croatian immunological society 2021 / - , 2021, 20-20

Skup
Annual Meeting of the Croatian Immunological Society 2021

Mjesto i datum
Trogir, Hrvatska, 23.09.2021. - 25.09.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
hepatic stellate cells ; Notch ; hepatic fibrosis ; CCL4 mouse model ; DDC-suplemented diet mouse model ; tamoxifen

Sažetak
Hepatic fibrosis is a common feature of various liver diseases characterized by activation of hepatic stellate cells (HSC), a principal source of alpha smooth muscle actin (αSMA) liver myofibroblasts. The pathophisiological role of Notch activation has been well established, but the role of Notch pathway in activated HSCs is still not sufficiently investigated. In the present research we first used two common murine models of liver fibrosis, carbon tetrachloride (CCL4) treatment for 6 weeks and 0.1% DDC- supplemented diet for 4 weeks to analyse expression of Notch-related genes. In CCL4 model, PCR analysis showed an upregulation of Notch2, Hey1, HeyL, and Jag2, while DDC-induced fibrosis was associated with increased expression of Notch2, Notch3, Hey1, Hes1, HeyL, Jag1 and Jag2. In the next set of experiments we used double transgenic SmaCre∆Rbpjκ∆ and SmaCreNICD1 mice in which Notch signaling pathway was specifically inhibited or activated in myofibroblasts by tamoxifen injections during the fibrosis development. However, Notch inhibition did not change significantly the degree of fibrosis, as evidenced by similar histological Sirius red liver staining and similar tissue expression of COL1A1 and ACTA2 between the control (SmaCre-∆Rbpjκ∆) and Notch inhibited (SmaCre+∆Rbpjκ∆) mice. Furthermore forcefull activation of Notch in myofibrroblasts did not change the degree of liver foibrosis. So far, our data do not support conclusion that Notch signaling in myofibroblasts contribute to liver fibrosis development in CCL4 and DDC model.

Izvorni jezik
Engleski

POVEZANOST RADA