Role of Protein Kinase a Pathway in Epidermal Growth Factor-Induced Liver Cell Repair

Minako Kikuchi, Thomas Y. Ma, Andrzej S. Tarnawski, Hiroshi Shimada, I. James Sarfeh

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


To gain a better understanding of the mechanisms that control the repair process in the injured liver, the actions of epidermal growth factor (EGF) and protein kinase A (PKA) were studied. Normal rat liver cells (clone 9) were grown to confluence. Standardized excisional wounds were made with a razor blade. The extent of hepatocyte migration into the wound was measured and determined at specific time intervals using a computerized digital analyzing system. Immunostaining of F-actin was performed with a fluorescein-labeled phalloidin. EGF significantly stimulated liver cell migration, whereas specific EGF-neutralizing antibody inhibited the EGF-induced migration. Agents that activate PKA at different stages of the PKA activation pathway, including 3-isobutyl-1-methylxanthine (IBMX), forskolin, and cholera toxin, inhibited EGF-induced migration. EGF triggered formation of actin stress fibers. PKA-activating agents inhibited actin stress fiber formation and stretching of cells at the wound margin. The following conclusions were drawn: (1) In excisional wounds of hepatocyte monolayers, both EGF and PKA exert action on actin microfilaments, which are stretched by EGF and inhibited by PKA; (2) the enhanced repair of wounded hepatocyte monolayers by EGF is blocked by activation of the PKA pathway at various levels; and (3) these actions of EGF and PKA indicate their important regulatory roles in controlling the rate of hepatocyte migration and restitution following the creation of excisional wounds.

Original languageEnglish (US)
Pages (from-to)132-137
Number of pages6
JournalJournal of Gastrointestinal Surgery
Issue number2
StatePublished - 1997

All Science Journal Classification (ASJC) codes

  • Surgery
  • Gastroenterology


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