Differential expression of the trypsin inhibitor SPINK3 mRNA and the mouse ortholog of secretory granule protein ZG-16p mRNA in the mouse pancreas after repetitive injury.
A mouse model using repetitive acinar cell injury caused by supraphysiologic doses of cerulein to induce the characteristic fibrosis and loss of acinar cell mass found in human chronic pancreatitis was employed to identify early changes in gene expression. A gene array was used to detect changes in 18,000 expressed sequence tags; changes in specific transcripts were confirmed by RNase protection assays. These methods identified SPINK3, the mouse homologue of human and rat protease inhibitor genes, as being highly expressed in the pancreas and induced after pancreatic injury. Because SPINK3 may be an important serine protease inhibitor, its up-regulation may reflect an important endogenous cytoprotective mechanism in preventing further injury. The up-regulation of SPINK3 was specific; the mouse homologue of the zymogen-processing protein ZG-16p was also highly expressed in the pancreas but sharply down-regulated early in the course of injury. These findings suggest that the pancreatic acinar cell may respond to injury with a program of self-preservation and loss of normal function.
Neuschwander-Tetri
Brent A
BA
Liver Center, Saint Louis University School of Medicine, St. Louis, Missouri, USA. tetriba@slu.edu
Fimmel
Claus J
CJ
Kladney
Raleigh D
RD
Wells
Lisa D
LD
Talkad
Vanita
V
D000595:Amino Acid Sequence; D000818:Animals; D002108:Ceruletide; D002908:Chronic Disease; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D037102:Lectins / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D010179:Pancreas / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D029584:Prostatic Secretory Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014361:Trypsin Inhibitors / Q000096:biosynthesis / Q000235:genetics
D006023:Glycoproteins; D037102:Lectins; D008565:Membrane Proteins; D029584:Prostatic Secretory Proteins; D012333:RNA, Messenger; C487134:Spink1 protein, mouse; D014361:Trypsin Inhibitors; C487135:ZG-16 protein, mouse; C119740:ZG16 protein, rat; D014359:Trypsin Inhibitor, Kazal Pancreatic; D002108:Ceruletide