Organ-specific stress induces mouse pancreatic keratin overexpression in association with NF-kappa B activation

BH Zhong, Q Zhou, Diana Toivola, GZ Tao, EZ Resurreccion, MB Omary

Research output: Contribution to journalArticleScientificpeer-review

47 Citations (Scopus)


Keratin polypeptides 8 and 18 (K8/K18) are the major intermediate filament proteins of pancreatic acinar cells and hepatocytes. Pancreatic keratin function is unknown, whereas hepatocyte keratins protect from mechanical and non-mechanical forms of stress. We characterized steady-state pancreatic keratin expression in Balb/c mice after caerulein and choline-deficient ethionine-supplemented diet (CDD), or on exposure to the generalized stresses of heat and water immersion. Keratins were studied at the protein, RNA and organizational levels. Isolated acini were used to study the role of nuclear factor (NF)-kappaB using selective inhibitors. Keratins were found to be abundant proteins making up 0.2%, 0.3% and 0.5% of the total cellular protein of pancreas, liver and small intestine, respectively. Caerulein and CDD caused a threefold transcription-mediated overall increase in K8/K18/K19/ K20 proteins. Keratin overexpression begins on tissue recovery, peaks 2 days after caerulein injection, or I day after CDD discontinuation, and returns to basal levels after 10 days. K19/K20-containing cytoplasmic filaments are nearly absent pre-injury but form post-injury then return to their original membrane-proximal distribution after 10 days. By contrast, generalized stresses of heat or water-immersion stress do not alter keratin expression levels. Caerulein-induced keratin overexpression is associated with NF-kappaB activation when tested using ex vivo acinar cell cultures. In conclusion, keratins are abundant proteins that can behave as stress proteins in response to tissue-specific but not generalized forms of injury. Pancreatic keratin overexpression is associated with NF-kappaB activation and may serve unique functions in acinar or ductal cell response to injury.
Original languageUndefined/Unknown
Pages (from-to)1709–1719
Number of pages10
JournalJournal of Cell Science
Publication statusPublished - 2004
MoE publication typeA1 Journal article-refereed


  • water immersion
  • intermediate filaments
  • Pancreatitis
  • heat stress
  • keratins
  • caerulein
  • choline-deficient diet

Cite this