Figure 1

Expression of matriptase network in hepatic injury. (A) Real-time RT-PCR analysis. Elevated expression levels of Spint1, St14, Prss8, and Krt1-19 transcripts were particularly evident in the two liver injury protocols with HPC-responses. While Krt1-19 transcripts were significantly increased up to 7-fold on day 14 in the BDL protocol, HPC response showed the highest induction, with increases from 3- to 40-fold on days 1 through 9 in the AAF/PHx protocol and from 4- to 60-fold at weeks 1 through 4 in the CDE protocol. Similar expression patterns were obtained for St14 and Spint1 transcripts. Where St14 was increased 2.6- to 7-fold in the PHx and BDL protocols, a 45- to 90-fold increase was observed on week 4 in the CDE and on day 9 in the AAF/PHx protocols, respectively. Similarly, Spint1 reached a 90- to 105-fold increase on week 3 in the CDE and day 9 in AAF/PHx protocols, whereas Prss8 increased 16- to 18-fold, respectively. In control and sham protocols, significant changes in gene expression were not detected. Values are relative to the uninjured control group ± standard deviation (*P < 0.05; †P < 0.001). Very strong positive correlations were observed between expression values for Spint1 and St14 and the progenitor cell marker Krt1-19. (b) Triple immunofluorescence localized: (a) matriptase, (b) HAI-1, and (c) OV6/Krt19 to both the cholangiocytes and HPC response. (a-d) Dlk1 marked a subpopulation of matriptase or HAI-1-positive cells in the HPC response. (c,d) Nidogen1 closely encircled the tortuous structures in the HPC response. (e-g) HAI-1 was expressed by cholangiocytes and HPCs regardless of type of hepatic insult. Dlk1, however, was only located to a subpopulation of cells in the HPC response. Magnification: 10×; inserts 40×.