Increased expression of hypoxia-inducible factor-1alpha, p48, and the Notch signaling cascade during acute pancreatitis in mice.
Acute pancreatitis (AP) is a complex disease that may be linked to acinar cell apoptosis and inadequate acinar cell replacement. Differentiation of acinar cells is regulated by p48, a DNA binding subunit of the transcription factor PTF1, and the Notch signaling pathway. Acinar cell apoptosis is triggered by oxygen deprivation, ie, hypoxia, by activation of hypoxia inducible factor-1alpha (HIF-1alpha). The aim of this study was to characterize by Northern blot analyses expression of HIF-1alpha, HIF-1alpha-inducible genes (GLUT-1, VEGF, p53), p48, and genes involved in the Notch signaling pathway (Notch-1, Dll1, RBP-Jk, HES-1) during cerulein-induced AP in mice. Maximal expression of HIF-1alpha, HIF-1alpha-inducible genes, p48, and Notch signaling genes occurred 8-12 hours after induction of AP. Maximal expression of p53 occurred 12-48 hours after induction of AP. These findings demonstrate that multiple pancreatic genes are activated acutely during AP that support pancreatic cell replenishment, regulation of expression of acinar cell-specific genes, and apoptosis.
Gomez
Guillermo
G
Department of Surgery, The University of Texas Medical Branch, Galveston, Texas 77555-0725, USA.
Englander
Ella W
EW
Wang
Guiyun
G
Greeley
George H
GH
D000208:Acute Disease; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D015152:Blotting, Northern; D002108:Ceruletide; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics; D010195:Pancreatitis / Q000139:chemically induced / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface / Q000235:genetics; D051880:Receptors, Notch; D015398:Signal Transduction / Q000235:genetics*; D013997:Time Factors; D000072056:Transcription Factor HES-1; D014157:Transcription Factors / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D002108:Ceruletide; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D008565:Membrane Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; C489734:Hes1 protein, mouse; C497762:Notch1 protein, mouse; C497571:Rbpj protein, mouse; C062602:transcription factor PTF1