title: Stanniocalcin 2 alters PERK signalling and reduces cellular injury during cerulein induced pancreatitis in mice.
abstract: BACKGROUND
  Stanniocalcin 2 (STC2) is a secreted protein activated by (PKR)-like Endoplasmic Reticulum Kinase (PERK) signalling under conditions of ER stress in vitro. Over-expression of STC2 in mice leads to a growth-restricted phenotype; however, the physiological function for STC2 has remained elusive. Given the relationship of STC2 to PERK signalling, the objective of this study was to examine the role of STC2 in PERK signalling in vivo.
  
  
  RESULTS
  Since PERK signalling has both physiological and pathological roles in the pancreas, STC2 expression was assessed in mouse pancreata before and after induction of injury using a cerulein-induced pancreatitis (CIP) model. Increased Stc2 expression was identified within four hours of initiating pancreatic injury and correlated to increased activation of PERK signalling. To determine the effect of STC2 over-expression on PERK, mice systemically expressing human STC2 (STC2Tg) were examined. STC2Tg pancreatic tissue exhibited normal pancreatic morphology, but altered activation of PERK signalling, including increases in Activating Transcription Factor (ATF) 4 accumulation and autophagy. Upon induction of pancreatic injury, STC2Tg mice exhibited limited increases in circulating amylase levels and increased maintenance of cellular junctions.
  
  
  CONCLUSIONS
  This study links STC2 to the pathological activation of PERK in vivo, and suggests involvement of STC2 in responding to pancreatic acinar cell injury.
authors.affiliation: Department of Paediatrics, The University of Western Ontario, London, Ontario, N6A 3K7, Canada.
authors.forename: Elena N
authors.initials: EN
authors.lastname: Fazio
authors.forename: Gabriel E
authors.initials: GE
authors.lastname: Dimattia
authors.forename: Sami A
authors.initials: SA
authors.lastname: Chadi
authors.forename: Kristin D
authors.initials: KD
authors.lastname: Kernohan
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Pin
mesh_terms: D051701:Activating Transcription Factor 4 / Q000378:metabolism; D000681:Amylases / Q000097:blood; D000818:Animals; D001343:Autophagy; D002108:Ceruletide / Q000633:toxicity; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism*
chemical_list: D051701:Activating Transcription Factor 4; D000681:Amylases; D002108:Ceruletide; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019892:eIF-2 Kinase; C485438:Stc2 protein, mouse