GCLM and cirrhosis of liver: Specifically, these workers reported that experimental liver cirrhosis, caused by CCl4, resulted in increases in Xbp1s and its downstream target Hrd1, which in turn stimulated ubiquitylation and degradation of Nrf2, thereby decreasing expression of Nqo1 and Gclm. In the present study, we discovered chronic feeding of Nrf2+/+ mice with the HFFr diet stimulated ER stress in the liver, with clear evidence of activation of the Xbp1 arm (Figure 10A and B).