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TGF-β1 Signaling Activates Hepatic Stellate Cells Through Notch Pathway

TGF-β1 Signaling Activates Hepatic Stellate Cells Through Notch Pathway

Yasen Aimaiti, Maimaitinijiati Yusufukadier, Wending Li, Tusun Tuerhongjiang, Apar Shadike, Aisan Meiheriayi, Gulisitan, Aini Abudusalamu, Hui Wang, Aji Tuerganaili, Yingmei Shao, Hao Wen

Cytotechnology. 2019 Oct;71(5):881-891.

PMID: 31372876

Abstract:

Hepatic stellate cells (HSCs), as the most important stromal cells in the liver microenvironment, play crucial roles in hepatic fibrosis, hepatocellular carcinoma, liver regeneration and fetal liver development after transdifferentiating into myofibroblasts (MFs). Transforming growth factor β1 (TGF-β1), as an important polyergic cytokine, is involved in HSCs activation process. However, the specific mechanisms of HSCs transdifferentiation process are not clearly demonstrated. Here we added exogenous recombinant TGF-β1 protein and transforming growth factor β receptor 1 (TGF-βR1) inhibitor SB431542 into mouse HSCs to detect the detailed impact of TGF-β1 signaling on HSCs activation. TGF-β1 signaling significantly increased phosphorylated (P)-Smad2/3 level and promoted Smad2/3 translocation from the cytoplasm to the nucleus, which also caused transdifferentiation of HSCs into MFs. Importantly, TGF-β1 signaling also resulted in high expression of Notch pathway markers Notch1, Jagged1, Hes1 in HSCs. In contrast, expression of those above markers in mouse HSCs were obviously decreased after hampering TGF-β1 signaling via TGF-βR1 inhibitor SB431542. To further examine the effect of Notch pathway on HSCs activation process, TGF-β1-stimulated HSCs and control HSCs were treated with or without LY450139, a specific inhibitor of Notch pathway. LY450139 evidently decreased the expression of Notch1 and MFs marker α-smooth muscle actin (α-SMA) expression in HSCs. These above results may provide a novel insight that TGF-β1 signaling controls HSCs activation process through regulating the expression of Notch pathway markers.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP425386603	LY450139		425386-60-3	Price

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