Fibroblast Growth Factor 5 Promotes the Proliferation of Corneal Epithelium Through Phosphoinositide 3-Kinase/Protein Kinase B Signaling Pathway Activation

Abstract

The recovery of corneal epithelial wounds is a complex process involving several physiological and pathological mechanisms that require further investigation. Our study has unveiled that the primary expression of FGF5 and FGFR1 occurs in the basal epithelium of the limbus. In the early 48 hours of the corneal epithelial wound healing process, FGF5 expression gradually rose and subsequently returned to baseline levels. The mice corneal epithelial cells (TKE2) proliferation was promoted by rhFGF5. Furthermore, the stemness-related genes K14, K15, P63, and the proliferation marker Ki67 levels expression increased after treatment with rhFGF5. In vivo, rhFGF5 promoted corneal epithelial wound healing. The RNA sequencing analysis of rhFGF5 treated TKE2 cells revealed 1512 differentially expressed genes. Different genes related to the cell cycle, proliferation, and regulatory signaling pathways were enriched. Moreover, the activation of the phosphoinositide 3-kinase/protein kinase B (PI3K-AKT) signaling pathway due to FGF5 led to the amplification of corneal progenitor cells. When FGF5 expression was curbed using siRNA, both proliferation and PI3K-AKT signaling pathway activation decreased. Our investigation has demonstrated that FGF5 stimulates the expansion of corneal limbal stem cells by activating the PI3K-AKT signaling pathway. Therefore, FGF5 has the potential to be an efficacious therapeutic intervention for treating corneal epithelial injuries.