Amelioration of hepatic fibrosis by CDDO-Me in NASH mice
Nrf2 activation has been reported to inhibit the hepatic fibrosis
induced by HSC activation through inhibition of the TGFβ/Smad pathway
(Oh et al., 2012; Prestigiacomo & Suter-Dick, 2018). Collagen fibres,
which are a marker of fibrosis formation detected by Sirius red
staining, were significantly increased in the livers of CDAHFD-fed mice
compared with those in control livers, consistent with the αSMA staining
observed in HSC activation (Figure 4a). CDDO-Me treatment markedly
reduced the positive staining results (Figure 4a). Accumulation of
hydroxyproline, a major component of collagen in NASH, was significantly
inhibited by treatment with CDDO-Me compared to that in the
vehicle-treated CDAHFD-fed mice (Figure 4b). The expression levels ofTgfb and other profibrotic markers, Acta2, Col1a1, Mmp2,
Mmp9, Mmp14, and Timp1 were significantly upregulated in
CDAHFD-fed mice in a dose-dependent manner when treated with CDDO-Me
(Figure 4c-e and Figure S5). The protein levels of αSMA were also
consistent with the immunohistochemical data (Figure 4f, g and Figure
S4). These results indicate that CDDO-Me inhibits the hepatic fibrosis
induced by HSC activation. All of full-length blot images were shown in
Figure S4.