Noggin attenuates cerulein-induced acute pancreatitis and impaired autophagy

Yanna Cao, Wenli Yang, Matthew A. Tyler, Xuxia Gao, Chaojun Duan, Sung O. Kim, Judith Aronson, Vsevolod Popov, Hitoshi Takahashi, Hiroshi Saito, Bernard Mark Evers, Celia Chao, Mark Hellmich, Tien C. Ko

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Objective: To investigate the role of bone morphogenetic protein (BMP) signaling in acute pancreatitis (AP) by administration of noggin, an endogenous BMP antagonist, in a cerulein-induced AP model. METHODS: Acute pancreatitis was induced by 9 hourly intraperitoneal injections of cerulein (50 μg/kg). Control mice received phosphate-buffered saline injections. In a separate group, noggin (0.5 mg/kg) was given intraperitoneally at 1 hour before and 2, 4, and 6 hours after AP induction. The mice were euthanized at 1 hour after completion of AP induction. The blood samples and the pancreas were harvested for analysis. Isolated pancreatic acini from normal mice and AR42J cells were treated with BMP2 and cerulein. AR42J cells were also treated with noggin. Phosphorylation of Smad1/5/8 was measured. RESULTS: Bone morphogenetic protein signaling was up-regulated in AP mouse pancreas. Bone morphogenetic protein 2 and cerulein-induced phosphorylation of Smad1/5/8 in the acinar cells in vitro, which was blocked by noggin.Noggin administration in vivo attenuated AP induction, decreased vacuole formation in acinar cells, blocked LC3-II levels, and partially restored Beclin-1 and lysosomal-associated membrane protein 2 levels. CONCLUSIONS: Bone morphogenetic protein signaling seems to promote AP induction and autophagy, as suggested by our study showing that noggin ameliorates AP and partially restores autophagic homeostasis.

Original languageEnglish (US)
Pages (from-to)301-307
Number of pages7
JournalPancreas
Volume42
Issue number2
DOIs
StatePublished - Mar 2013

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Keywords

  • acute pancreatitis
  • autophagy
  • cerulein
  • noggin

ASJC Scopus subject areas

  • Hepatology
  • Internal Medicine
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Cao, Y., Yang, W., Tyler, M. A., Gao, X., Duan, C., Kim, S. O., Aronson, J., Popov, V., Takahashi, H., Saito, H., Evers, B. M., Chao, C., Hellmich, M., & Ko, T. C. (2013). Noggin attenuates cerulein-induced acute pancreatitis and impaired autophagy. Pancreas, 42(2), 301-307. https://doi.org/10.1097/MPA.0b013e31825b9f2c