ATF4 and chronic kidney disease: Under uremic toxin conditions, activation of the ER stress-mediated signaling pathway, including GRP78, p-PERK, p-IRE1α, and ATF4, was significantly increased in SH-SY5Y cells co-cultured with CKD-hMSCs, compared with those co-cultured with normal hMSCs (Figure 3C,D).