title: Extensive pancreas regeneration following acinar-specific disruption of Xbp1 in mice.
abstract: OBJECTIVE
  Progression of diseases of the exocrine pancreas, which include pancreatitis and cancer, is associated with increased levels of cell stress. Pancreatic acinar cells are involved in development of these diseases and, because of their high level of protein output, they require an efficient, unfolded protein response (UPR) that mediates recovery from endoplasmic reticulum (ER) stress following the accumulation of misfolded proteins.
  
  
  METHODS
  To study recovery from ER stress in the exocrine organ, we generated mice with conditional disruption of Xbp1 (a principal component of the UPR) in most adult pancreatic acinar cells (Xbp1fl/fl). We monitored the effects of constitutive ER stress in the exocrine pancreas of these mice.
  
  
  RESULTS
  Xbp1-null acinar cells underwent extensive apoptosis, followed by a rapid phase of recovery in the pancreas that included expansion of the centroacinar cell compartment, formation of tubular complexes that contained Hes1- and Sox9-expressing cells, and regeneration of acinar cells that expressed Mist1 from the residual, surviving Xbp1+ cell population.
  
  
  CONCLUSIONS
  XBP1 is required for homeostasis of acinar cells in mice; ER stress induces a regenerative response in the pancreas that involves acinar and centroacinar cells, providing the needed capacity for organ recovery from exocrine pancreas disease.
authors.affiliation: Department of Biological Sciences and the Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907-2064, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Hess
authors.forename: Sean E
authors.initials: SE
authors.lastname: Humphrey
authors.forename: Jeff
authors.initials: J
authors.lastname: Ishibashi
authors.forename: Barbara
authors.initials: B
authors.lastname: Damsz
authors.forename: Ann-Hwee
authors.initials: AH
authors.lastname: Lee
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Glimcher
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Konieczny
mesh_terms: D000818:Animals; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D019070:Cell Lineage; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000473:pathology; D018398:Homeodomain Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D046790:Pancreas, Exocrine / Q000378:metabolism* / Q000473:pathology; D010182:Pancreatic Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012038:Regeneration; D000071701:Regulatory Factor X Transcription Factors; D055758:SOX9 Transcription Factor / Q000378:metabolism; D013312:Stress, Physiological; D013997:Time Factors; D000072056:Transcription Factor HES-1; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics; D056811:Unfolded Protein Response; D000071717:X-Box Binding Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; D000071701:Regulatory Factor X Transcription Factors; D055758:SOX9 Transcription Factor; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C491312:Bhlha15 protein, mouse; C489734:Hes1 protein, mouse; C527933:Sox9 protein, mouse; C000605544:Xbp1 protein, mouse; C486556:Ern2 protein, mouse