Naslov
The role of Notch signaling in carbon tetrachloride murine model of hepatic fibrosis

Autori
Šisl, Dino ; Novak, Sanja ; Kalajzić, Ivo ; Filipović, Maša ; Lukač, Nina ; 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 2020: [programme and abstract book] / - Rijeka : Hrvatsko imunološko društvo, 2020, 46-46

Skup
Annual meeting of the Croatian Immunological Society 2020

Mjesto i datum
Online, 01.10.2020. - 02.10.2020

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

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

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. Recent studies suggested a possible role of Notch signaling pathway in pathogenesis of fibrosis. In our research, we have studied the expression of Notch-related molecules during fibrogenesis and analyzed contribution of various αSMA+ cell populations to the pool of liver myofibroblasts. Common murine model of liver fibrosis, 6- week carbon tetrachloride (CCl4) treatment, was used. PCR analysis of whole liver tissue showed upregulation of genes for Hey1, HeyL, Notch2 and Jag2, while downregulation of Notch1 and Notch4, and upregulation of Notch2 was shown on isolated HSCs. Notch1 downregulation in HSCs was further confirmed by flow cytometry where it was shown that 42.3% of freshly isolated HSCs from normal mice express Notch1, whereas only 13.9% of those from fibrotic liver express it. We used tamoxifen inducible Cre mice (αSMA- CreERT2/Ai9) to assess contribution of various αSMA+ cell populations to myofibroblast pool. In normal, nonfibrotic liver, only vascular smooth muscle cells (VSMCs) were labeled after tamoxifen application. In further experiments, tamoxifen was given either before (to label VSMCs) or after (to label activated HSCs and VSMCs) the initiation of CCl4 treatment. Immunohistochemical analysis excluded VSMCs as a major source of myofibroblasts in fibrosis and confirmed that majority of myofibroblasts stem from activated HSCs. In the upcoming experiments we aim to modulate Notch signaling pathway specifically in αSMA+ cells to clarify its importance in fibrotic processes.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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