Reduced expression of epidermal growth factor receptors in rat liver during aging

Amrita Kamat, Paramita M Ghosh, Renee L. Glover, Bing Zhu, Chih Ko Yeh, Goutam Ghosh Choudhury, Michael S. Katz

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Proliferative responsiveness of hepatocytes to epidermal growth factor (EGF) declines during aging. The role of EGF receptors in mediating age-dependent changes of EGF-induced mitogenic signaling in liver remains incompletely understood. We assessed EGF receptor expression levels in whole liver specimens as well as in freshly isolated and cultured hepatocytes from young adult and senescent Fischer 344 male rats. Hepatic EGF receptor messenger RNA and protein levels, and the number of high- and low-affinity receptor binding sites, decreased with aging. Ligandinduced EGF receptor activation, determined by receptor dimerization and tyrosine phosphorylation, was reduced in old animals in parallel with the age-related decline in receptor expression. Stimulation of the extracellular signal-regulated kinase pathway by EGF was also attenuated in hepatocytes from old animals. Our results implicate decreased expression of EGF receptors as a key determinant of reduced mitogenic signaling responsive to EGF stimulation of liver during aging.

Original languageEnglish (US)
Pages (from-to)683-692
Number of pages10
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume63
Issue number7
StatePublished - Jul 2008

Keywords

  • Extracellular signal-regulated kinase
  • Hepatocytes
  • Receptor dimerization
  • Receptor tyrosine kinase

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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