Naslov
The role of Notch signaling in murine models of fibrogenesis

Autori
Šisl, Dino ; Novak, Sanja ; Kalajzić, Ivo ; Filipović, Maša ; Lukač, Nina ; Flegar, Darja ; Bekan, Ivan Budimir ; Kovačić, Nataša ; Grčević, Danka ; Markotić, Antonio ; Kelava, Tomislav

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

Skup
Annual meeting of the Croatian Immunological Society 2019

Mjesto i datum
Rovinj, Hrvatska, 11.10.2019. - 12.10.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
hepatic fibrosis, hepatic stellate cells, Notch signalling pathway, murine model of hepatic 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. Recent studies suggested a possible role of Notch signaling pathway in pathogenesis of fibrosis. In the present research we have studied the expression of Notch- related molecules during the fibrogenesis and analyzed contribution of various αSMA positive cell populations to the pool of liver myofibroblasts. Two common murine models of liver fibrosis, carbon tetrachloride (CCL4) treatment for 6 weeks and 0.1% DDC-supplemented diet for 4 weeks were used. PCR analysis showed an upregulation of various Notch-related genes in both models. In CCL4 model, Hey1, HeyL, Notch2 and Jag2 were upregulated, while DDC-induced fibrosis was associated with increased expression of Hey1, Hes1, HeyL, Notch2, Notch3, Jag1 and Jag2. We used tamoxifen inducible Cre mice (αSMA-CreERT2/Ai9) to asses 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 elucidate its importance in fibrotic processes.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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