Fig. 5: ER stress-mediated activation of cathepsin B is responsible for the Srxn1 inhibition-mediated effects.

A Administration of cerulein via 8-hourly or 12-hourly injections led to significantly increased expression of p-PERK, XBP1s, and ATF4 in pancreatic tissues. B The transcriptomic profiles of acinar cells with Srxn1 knockdown or control stimulated by cerulein (50 nM) for 6 h. C GSEA showed that siRNA led to the enrichment of apoptosis, TNF, and protein-processing signaling pathways in acinar cells. D siRNA led to markedly increased expression of ER stress markers in acinar cells. E J14 significantly induced ER stress upon stimulation with cerulein compared to cerulein alone in mice. F Sal003 induces ATF4 expression, and GSK2606414 inhibits p-PERK and ATF4 expression. G Activation of ER stress by Sal003 facilitated apoptosis, while inhibition of ER stress by GSK2606414 inhibited apoptosis in acinar cells. In the presence of J14, inhibition of ER stress alleviated apoptosis nearly to the level of the cerulein group. H, I Sal003 increased trypsin activity, while GSK2606414 decreased trypsin activity in acinar cells. J Cathepsin B RNA expression was decreased by cerulein and Srxn1 siRNA. K Cerulein activated CTSB, which could be further enhanced by J14. L Inhibition of ER stress alleviated the activation of CTSB, while inducing ER stress markedly promoted the activation of CSTB in acinar cells. Con control; *p < 0.05, **p < 0.01, ***p < 0.001. Data represent three or more experiments for in vitro assays and eight for in vivo assays.