High mobility group box 1 induces the activation of the Janus kinase 2 and signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in pancreatic acinar cells in rats, while AG490 and rapamycin inhibit their activation

  • Guoliang Wang Department of Hepatobiliary Surgery, Guizhou Provincial People’s Hospital, Guiyang, China
  • Jingchao Zhang Department of Anesthesiology, Guizhou Provincial People’s Hospital, Guiyang, China
  • Danhua Dui Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Zunyi Medical College, Zunyi, China
  • Haoyuan Ren Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Zunyi Medical College, Zunyi, China
  • Jin Liu Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Zunyi Medical College, Zunyi, China
Keywords: Rat pancreatic acinar cells, high mobility group box 1, Janus kinase 2, signal transducer and activator of transcription 3, AG490, rapamycin

Abstract

The pathogenesis of severe acute pancreatitis (SAP) remains unclear. The Janus kinase and signal transducer and activator of transcription (JAK/STAT) pathway is important for various cytokines and growth factors. This study investigated the effect of the late inflammatory factor high mobility group box 1 (HMGB1) on the activation of JAK2/STAT3 in pancreatic acinar cells and the inhibitory effects of AG490 (a JAK2 inhibitor) and rapamycin (a STAT3 inhibitor) on this pathway. Rat pancreatic acinar cells were randomly divided into the control, HMGB1, AG490, and rapamycin groups. The mRNA levels of JAK2 and STAT3 at 10, 30, 60, and 120 minutes were detected using reverse transcription polymerase chain reaction (RT-PCR). The protein levels of JAK2 and STAT3 at 60 and 120 minutes were observed using Western blotting. Compared with the control group, the HMGB1 group exhibited significantly increased levels of JAK2 mRNA at each time point; STAT3 mRNA at 30, 60, and 120 minutes; and JAK2 and STAT3 proteins at 60 and 120 minutes (p < 0.01). Compared with the HMGB1 group, the AG490 and rapamycin groups both exhibited significantly decreased levels of JAK2 mRNA at each time point (p < 0.05); STAT3 mRNA at 30, 60, and 120 minutes (p < 0.01); and JAK2 and STAT3 proteins at 60 and 120 minutes (p < 0.01). HMGB1 induces the activation of the JAK2/STAT3 signaling pathway in rat pancreatic acinar cells, and this activation can be inhibited by AG490 and rapamycin. The results of this study may provide new insights for the treatment of SAP.

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Author Biographies

Guoliang Wang, Department of Hepatobiliary Surgery, Guizhou Provincial People’s Hospital, Guiyang, China
Department of Hepatobiliary Surgery
Jingchao Zhang, Department of Anesthesiology, Guizhou Provincial People’s Hospital, Guiyang, China
Department of Anesthesiology
Danhua Dui, Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Zunyi Medical College, Zunyi, China
Department of Hepatopancreatobiliary Surgery
Haoyuan Ren, Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Zunyi Medical College, Zunyi, China
Department of Hepatopancreatobiliary Surgery
Jin Liu, Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Zunyi Medical College, Zunyi, China
Department of Hepatopancreatobiliary Surgery

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Published
2016-11-10
How to Cite
1.
Wang G, Zhang J, Dui D, Ren H, Liu J. High mobility group box 1 induces the activation of the Janus kinase 2 and signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in pancreatic acinar cells in rats, while AG490 and rapamycin inhibit their activation. Bosn J of Basic Med Sci [Internet]. 2016Nov.10 [cited 2019Nov.18];16(4):307-12. Available from: https://bjbms.org/ojs/index.php/bjbms/article/view/1442
Section
Translational and Clinical Research