Effect of Janus activated kinase 2/signal transducer and activators of transcription 3 signaling pathway on the release of high mobility group box 1 in trypsinogen activation peptide-induced rat pancreatic acinar cells

Abstract

Objective To research the effect of Janus activated kinase 2/signal transducer and activators of transcription 3 (JAK2/STAT3) signaling pathway on the release of high mobility group box 1 (HMGB1) in trypsinogen activation peptide (TAP)-induced rat pancreatic acinar cells.Methods The rat pancreatic acinar cells were isolated,and randomly divided imo normal control group,TAP promotion group (3 nmol/L),AG490 treatment group (25 μ mol/L) and RPM treatment group (40 μg/L).Within 3-24 h the HMGB1 mRNA and protein expression levels were detected by using PCR and Western blotting.Results In comparison with the normal control group (1.01 ± 0.04),HMGB1 mRNA expression was significantly increased at 6,12 and 24 h in TAP promotion group (2.87 ±0.08,32.85 ± 1.48 and 38.43 ±1.60,P ＜0.01 for all),that was dramatically inhibited at 12 and 24 h in AG490 treatment group as compared with TAP promotion group (23.40 ± 1.38 and 19.44 ± 0.89,P ＜ 0.01 for all),and that was dramatically inhibited at 12 and 24 h in RPM treatment group as compared with TAP promotion group (21.14 ± 1.32 and 17.76 ± 0.57,P＜ 0.01 for all).In comparison with the normal control group (0.39 ±0.02),the HMGB1 expression was significantly increased at 3,6,12 h and 24 h in TAP promotion group (0.46 ± 0.02,0.67 ± 0.03,0.72 ± 0.02 and 0.90 ± 0.03,P ＜ 0.01 for all),that was dramatically inhibited at 12 and 24 h in AG490 treatment group as compared with TAP promotion group (0.60 ±0.02 and 0.54 ±0.01,P ＜0.01 for all),and that was dramatically inhibited at 12 and 24 h in RPM treatment group as compared with TAP promotion group (0.59 ± 0.02 and 0.58 ± 0.01,P ＜ 0.01 for all).Conclusion TAP induces rat pancreatic acinar cells to release HMGB1,which is related to intracellular JAK2/STAT3 signaling pathway. Key words: Pancreatic acinar cells; Trypsinogen activation peptide; Highly-mobility group box-1 ; Janus activated kinase 2 ; Rapamycin