Simple epithelial keratins are dispensable for cytoprotection in two pancreatitis models

Pancreatic acinar cells express keratins 8 and 18 (K8/18), which form cytop lasmic filament (CF) and apicolateral filament (ALF) pools. Hepatocyte K8/1 8 CF provide important protection from environmental stresses, but disrupti on of acinar cell CF has no significant impact. We asked whether acinar cel l ALF are important in providing cytoprotective roles by studying keratin f ilaments 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 ac inar cells also express apicolateral keratin 19 (K19), which explains the p resence of apicolateral keratins in K18-null pancreas. K8- and K18-null pan creata are histologically normal, and their acini respond similarly to stim ulated 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 norma l and K18-null acini, K19 is upregulated after caerulein injury and, unexpe ctedly, forms CF. As in hepatocytes, acinar injury is also associated with keratin hyperphosphorylation. Hence, K19 forms ALF in mouse acinar cells an d 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 c ytoprotection, in contrast to hepatocyte keratins, despite similar hyperpho sphorylation patterns after injury.