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. Author manuscript; available in PMC: 2012 Oct 1.
Published in final edited form as: Nat Med. 2012 Mar 4;18(4):572–579. doi: 10.1038/nm.2667

Figure 2. Modulation of the Notch pathway in vitro and in vivo affects biliary regeneration.

Figure 2

(a) mRNA expression of the NOTCH signalling pathway components in isolated ductular reactions of both hepatocellular and biliary patterns of disease. Immunohistochemistry for NOTCH2 and JAGGED1 with positivity during biliary disease (upper photomicrographs), however in hepatocellular regeneration only NOTCH2 protein is detectable (lower photomicrographs). (b) Notch pathway expression in murine models of biliary (upper photomicrographs) and hepatocellular (lower photomicrographs) regeneration; Notch1 protein (red) in the EpCAM positive biliary tree (green) and Jagged1 (red) in the surrounding ductular stromal αSMA positive fibroblasts (green). (c) mRNA expression of Notch targets and liver enriched transcription factors after inhibition of the Notch pathway with DAPT in direct co–cultures of mHPCs and myofibroblasts in vitro (d) Quantification of absolute mHPC numbers in animals treated with DAPT in vivo vs. vehicle alone control. (e) Expression of Notch pathway targets and liver enriched transcription factors in mHPCs isolated from DAPT treated animals vs. vehicle alone controls. Data is expressed as means ± S.E.M; *P < 0.05, ** P < 0.01, ***P <0.001. Human: PBC/PSC n = 10 HCV n = 6. Murine CDE n = 4 DDC n = 4. Scale bar = 50μm