Fig. 9: MANF depends on CK19 and Notch2 to promote hepatocytes-derived ICC. | Cell Death & Differentiation

Fig. 9: MANF depends on CK19 and Notch2 to promote hepatocytes-derived ICC.

From: Hepatic factor MANF drives hepatocytes reprogramming by detaining cytosolic CK19 in intrahepatic cholangiocarcinoma

Fig. 9

A Scheme for SBT-induced ICC after knockdown of Notch2 using AAVs. B Gross morphology of mice livers. C Liver-body weight ratio. n = 6, **P < 0.01. D HE staining of mice liver tissues. E Tumor number. n = 6, *P < 0.05. F Tumber area. n = 6, *P < 0.05. G, H The levels of Notch2, CK19, Ki67, and MANF in SBT-induced mice ICC after Notch2 knockdown detected by immunohistochemistry staining. n = 3, **P < 0.01, ***P < 0.001. I Effects of Notch2 knockdown on hepatocytes transformation in the liver tissues of SBT-induced ICC mice after MANF knockin. The hepatocytes were double labeled by tdTomato (red) and anti-CK19 (green) antibody. J Effects of Notch2 knockdown on the levels of HNF4α, CK7, CK19, MANF, and Notch2 in primary hepatocytes isolated from tdTomato MANF KI mice challenged with SBT for 2 weeks. n = 3, *P < 0.05, **P < 0.01, ***P < 0.001. K Effects of CK19 knockdown on the levels of CK7, Notch2, MANF, and CK19 in Hucct1 cells overexpressing MANF. n = 3, *P < 0.05, **P < 0.01, ***P < 0.001. L No interaction of MANF, CK19, and NICD2 in Hucct1 cells with MANF knockdown detected by Co-IP assay. The isotype IgG was used as a negative control.

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