Data from: Nrf2 ameliorates DDC-induced sclerosing cholangitis and biliary fibrosis and improves the regenerative capacity of the liver.

The Nrf2 pathway protects against oxidative stress and induces
regeneration of various tissues. Here, we investigated whether Nrf2
protects from sclerosing cholangitis and biliary fibrosis and
simultaneously induces liver regeneration. Diet containing
3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) was fed to Nrf2-KO mice
(Nrf2-/-), mice with liver-specific hyper-activated Nrf2 (HKeap1-/-) and
wild type (WT) littermates to induce cholangitis, liver fibrosis, and oval
cell expansion. HKeap1-/--mice were protected from almost all DDC-induced
injury compared to WT and Nrf2-/-. Liver injury in Nrf2-/- and WT mice was
mostly similar, albeit Nrf2-/- suffered more from DDC diet as seen for
several parameters. Nrf2 activity was especially important for the
expression of the hepatic efflux transporters Abcg2 and Abcc2-4, which are
involved in hepatic toxin elimination. Surprisingly, cell proliferation
was more enhanced in Nrf2-/-- but also HKeap1-/--mice compared to WT.
Interestingly, Nrf2-/--mice failed to sufficiently activate oval cell
expansion after DDC-treatment and showed almost no resident oval cell
population under control conditions. The resident oval cell population of
untreated HKeap1-/--mice was increased and DDC-treatment resulted in a
stronger oval cell expansion compared to WT. We provide evidence that Nrf2
activation protects from DDC-induced sclerosing cholangitis and biliary
fibrosis. Moreover, our data establish a possible role of Nrf2 in oval
cell expansion.