PPARγ is essential for TEC to alleviate ANIT-induced
experimental intrahepatic cholestasis
To further confirm the physiological roles of PPARγ in TEC-mediated
hepatic protection in vivo, Ad-shPPARγ was injected into C57BL/6J mice
via the tail vein. Next, the mice were treated with ANIT and/or TEC as
described in the experimental method. As expected, TEC did not exert
hepatic protection in ANIT-induced CLD of PPARγ deficient mice, which
was supported by the fact that there was no obvious difference in AST,
ALT, AP and necrosis area after TEC treatment in PPARγ-deficient mice
(Figure 7A and 7B). Quantification of the bile acid pool size showed
that there was no significant influence on the content of bile acid in
the liver, serum and feces of PPARγ-deficient mice after TEC treatment
(Figure 7C). ANIT treatment alone markedly promoted macrophage
recruitment compared with NC, as evidenced by a significant increase in
F4/80 mRNA level in the liver (Figure 7D). The mRNA levels of
proinflammatory factors (Figure 7E) and profibrogenesis factors (Figure
7F) also supported these findings. PPARγ deficiency aggravated
inflammation in mouse liver, as shown by increased F4/80,
proinflammatory factors and profibrogenesis factors compared with ANIT
treatment alone, while TEC did not significantly decrease these genes in
PPARγ deficient mice. Furthermore, the expression of FXR and LXR in
mouse liver was analyzed, and the results showed that TEC did not
enhance the expression of FXR, LXR and bile transporters in
PPARγ-deficient mice (Figure 7G and 7H). Taken together, the lack of
PPARγ expression abolished hepatic protection by TEC.