| First Author | Peng H | Year | 2013 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 54 |
| Issue | 4 | Pages | 2781-6 |
| PubMed ID | 23548624 | Mgi Jnum | J:215295 |
| Mgi Id | MGI:5605002 | Doi | 10.1167/iovs.12-11512 |
| Citation | Peng H, et al. (2013) FIH-1/c-kit signaling: a novel contributor to corneal epithelial glycogen metabolism. Invest Ophthalmol Vis Sci 54(4):2781-6 |
| abstractText | 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)-3beta 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 Kit(W/Wv) mice were stained with periodic acid Schiff (PAS) to detect glycogen. RNA samples prepared from laser-capture 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-3beta 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. |
