Naslov
What is the role of Notch1 in liver fibrosis development?

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

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

Izvornik
European journal of immunology, 51 (2021), Suppl 1 / - , 2021, 305-305

Skup
6th European congress of immunology (ECI 2021)

Mjesto i datum
Online, 01.09.2021. - 04.09.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
animal models ; biology of the immune system ; chronic inflammation and fibrosis

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 pathophysiological role of Notch activation has been well established, but the role of Notch1 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 the expression of Notch‐related genes. In CCL4 model, qPCR 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∆ mice in which Notch1 signalling pathway was specifically inhibited in myofibroblasts by tamoxifen injections during the fibrosis development. Notch1 inhibition, however, did not change the degree of liver fibrosis, as evidenced by no significant difference in histological score on Sirius red liver staining and no difference in tissue expression of COL1A1 and ACTA2 between the control (SMACre‐∆Rbpjκ∆) and Notch1 inhibited (SmaCre+∆Rbpjκ∆) mice. So far, our data show that canonical Notch1 signalling in myofibroblasts is not a crucial contributor to liver fibrosis development in CCL4 and DDC model.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA