Keratinocyte Growth Factor Protects Retinal Pigment Epithelium Cells From Oxidative Injuries:A Mechanism Study

Aims: To understand the potential effect of keratinocyte growth factor(KGF)on Ultra-violet-induced damages in retinal pigment epithelium cells,and to study the underlying mechanisms.Research methods and contents: We used Western blot and real-time quantitative PCR to detect whether keratinocyte growth factor receptor(KGFR)m RNA and protein were expressed in human RPE cells;After pretreatment with KGF,we gave RPE cells UV radiation to observe the cell survival rate and apoptosis;KGF was added to RPE cells,and the activation of the downstream nuclear transcription related factor 2(Nrf2)and Akt-mTORC1 pathway was detected by Western blot and real-time quantitative polymerase chain reaction(PCR);Nrf2 was inhibited by Nrf2 sh RNAs or serine 40(S40T)mutation,KGF-induced RPE cell protection was analyzed when Nrf2 was inhibited;RAD001 and LY294002 were added to block Akt-mTORC1 signaling activation,KGF-induced RPE cell protection was tested;The changes in the protective effect of KGF induced RPE cells after blocking Akt-mTORC1 and Nrf2 pathways were observed.Results:(1)Expression of KGFR m RNA and protein in human RPE cells.(2)Pre-treatment with KGF inhibited UV-induced reactive oxygen species(ROS)production and RPE cell death;(3)KGF preconditioning inhibits apoptosis and non apoptotic death induced by UV in RPE cells;(4)KGF activated nuclear-factor-E2-related factor 2(Nrf2)signaling in RPE cells;(5)KGF preconditioning inhibits UV induced oxidative stress damage in RPE cells;(6)Nrf2 knockdown(by targeted sh RNAs)or serine 40 mutation blocked KGF-induced Nrf2 activation;(7)Nrf2 sh RNAs or serine 40(S40T)mutation blocked the protection of RPE cells induced by KGF;(8)Akt-mTORC1 blockage not only blocked KGF-induced Nrf2 activation,but also nullified KGF-mediated RPE cell protection against UV.Conclusions : KGF activates the Akt-mTORC1 dependent Nrf2 pathway to antagonize oxidative stress damage in RPE cells.