Stanniocalcin 2 alters PERK signalling and reduces cellular injury during cerulein induced pancreatitis in mice
1 Department of Paediatrics, The University of Western Ontario, 1151 Richmond Street, London, Ontario, N6A 3K7, Canada
2 Department of Physiology and Pharmacology, The University of Western Ontario, 1151 Richmond St., London, Ontario, N6A 3K7, Canada
3 Department of Biochemistry, The University of Western Ontario, 1151 Richmond St., London, Ontario, N6A 3K7, Canada
4 Department of Oncology, The University of Western Ontario, 1151 Richmond St., London, Ontario, N6A 3K7, Canada
5 Children's Health Research Institute, 800 Commissioners Rd. E, London, Ontario, N6C 2V5, Canada
6 London Regional Cancer Program, 790 Commissioners Rd. E., London, Ontario, N6C 2V5, Canada
BMC Cell Biology 2011, 12:17 doi:10.1186/1471-2121-12-17Published: 5 May 2011
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.
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.
This study links STC2 to the pathological activation of PERK in vivo, and suggests involvement of STC2 in responding to pancreatic acinar cell injury.