Dm. Toivola et al., Simple epithelial keratins are dispensable for cytoprotection in two pancreatitis models, AM J P-GAST, 279(6), 2000, pp. G1343-G1354
Citations number
46
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
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.