Fig. 5

Crenigacestat reduces iCCA hCAFs activation in PDX tissues. Panel A. TGFB1 as predicted upstream regulator and its target molecules by Ingenuity Pathway Analysis (IPA) in treated vs. untreated PDX tissues. Genes in red denote upregulation and downregulation in response to the treatment in green. Lines in orange denote predicted activation; lines in blue predict inhibition. Panel B. Crenigacestat downregulates α-SMA expression in PDX-treated mice, as detected by immunofluorescence staining. Vimentin (green) and α-SMA (red) in overlapping stains (yellow) co-immunolocalize in PDX tissues. The scale bar represents 50 μm. Panel C. The staining quantification was calculated as the mean intensity fluorescence of three images/tissue from PDX mice treated with Crenigacestat compared to the vehicle. ***p < 0.0001. Magnifications: 40X