FIH-1/c-kit signaling: A novel contributor to corneal epithelial glycogen metabolism

Han Peng, Julia Katsnelson, Wending Yang, Melissa Ann Brown, Robert M Lavker

Research output: Contribution to journalArticle

8 Scopus citations


PURPOSE. Corneal epithelial cells have large stores of glycogen, which serve as their primary energy source. Recently, we demonstrated that factor-inhibiting hypoxia-inducible factor 1 (FIH-1) diminished glycogen stores in vitro and in vivo, working through the Akt/Glycogen Synthase Kinase (GSK)-3b pathway. In this study we investigated the relationship between FIH-1 and c-kit as it pertains to limbal and corneal epithelial glycogen stores. METHODS. Limbal and corneal epithelia from wild-type FIH-1-/- and KitW/Wv mice were stained with periodic acid Schiff (PAS) to detect glycogen. RNA samples prepared from lasercapture microdissected populations of limbal epithelium were subjected to real-time quantitative PCR to determine c-kit ligand expression. Submerged cultures of primary human corneal epithelial keratinocytes (HCEKs) transduced with FIH-1 were treated with c-kit ligand to establish further a FIH-1/c-kit interaction via Western analysis. Akt phosphorylation was assessed by Western blotting. RESULTS. The limbal epithelial cells of FIH-1 null mice had an increase in glycogen levels as well as increased c-kit ligand mRNA compared with wild-type controls. Consistent with a FIH-1/c-kit association, the diminished Akt signaling observed in FIH-1-overexpressing HCEKs could be restored by the addition of c-kit ligand. Interestingly, Akt signaling and glycogen content of the corneal epithelium were significantly decreased in c-kit mutant mice. CONCLUSIONS. c-Kit signaling has been shown to affect glucose metabolism via the Akt/GSK-3β pathway. An inverse relationship between FIH-1 and c-kit signaling pathways accounts, in part, for differences in glycogen content between corneal and limbal epithelial cells.

Original languageEnglish (US)
Pages (from-to)2781-2786
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Issue number4
StatePublished - Apr 26 2013


  • Akt signaling
  • Energy metabolism
  • Keratinocytes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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