Simple epithelial keratins are dispensable for cytoprotection in two pancreatitis models.
Pancreatic acinar cells express keratins 8 and 18 (K8/18), which form cytoplasmic filament (CF) and apicolateral filament (ALF) pools. Hepatocyte K8/18 CF provide important protection from environmental stresses, but disruption of acinar cell CF has no significant impact. We asked whether acinar cell ALF are important in providing cytoprotective roles by studying keratin filaments in pancreata of K8- and K18-null mice. K8-null pancreas lacks both keratin pools, but K18-null pancreas lacks only CF. Mouse but not human acinar cells also express apicolateral keratin 19 (K19), which explains the presence of apicolateral keratins in K18-null pancreas. K8- and K18-null pancreata are histologically normal, and their acini respond similarly to stimulated secretion, although K8-null acini viability is reduced. Absence of total filaments (K8-null) or CF (K18-null) does not increase susceptibility to pancreatitis induced by caerulein or a choline-deficient diet. In normal and K18-null acini, K19 is upregulated after caerulein injury and, unexpectedly, forms CF. As in hepatocytes, acinar injury is also associated with keratin hyperphosphorylation. Hence, K19 forms ALF in mouse acinar cells and helps define two distinct ALF and CF pools. On injury, K19 forms CF that revert to ALF after healing. Acinar keratins appear to be dispensable for cytoprotection, in contrast to hepatocyte keratins, despite similar hyperphosphorylation patterns after injury.
Toivola
D M
DM
Department of Medicine, Palo Alto Veterans Affairs Medical Center and Stanford University, Palo Alto 94304, California, USA.
Baribault
H
H
Magin
T
T
Michie
S A
SA
Omary
M B
MB
D000199:Actins / Q000378:metabolism; D000818:Animals; D002470:Cell Survival; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007633:Keratins / Q000502:physiology*; D008297:Male; D051379:Mice; D010195:Pancreatitis / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation
D000199:Actins; D007633:Keratins