Distinct expression patterns of aging effects on the UPRER signaling pathway in rat colon and regulatory role of saponins from Panax japonicus.

Studies have reported that the unfolded protein response of ER (UPR^ER) declines in the several organs of aging mice. However, changes of UPR^ER during the aging process in the intestine are rarely reported. Our previous studies have demonstrated that Saponins from Panax japonicus (SPJ) have anti-aging effects in different murine models and can modulate ER stress. In the present study, we focused on age-dependent expressions of UPR^ER in the intestine of 6- to 24-month-old rats by an immunohistochemical (IHC) method and determined whether SPJ could regulate the three different UPR^ER branches of the colon in aging rats.

Aging rats had been treated with different doses (10 and 30 mg/kg) of SPJ for 6 months, which were mixed with feed, since they were 18 months old. Then the expressions of GRP78 and three different UPR^ER branches were determined by immunohistochemistry (IHC). Results: Total expressions of GRP78 and p-JNK increased, and other UPR^ER proteins decreased in the colon of aging rats, while SPJ treatment relieved the corresponding changes in aging rats. Here we also found different patterns of GRP78 and the three UPR^ER branches in the different layers of colon in rats.

The study demonstrated that UPR^ER declined and GRP78 increased in the colon of aging rats. SPJ could reverse most URP^ER changes in the colon of aging rats. This study also showed different expression patterns of the three branches of UPR^ER in different layers of the colon in rats.