Kisspeptin Suppresses the Growth of Primary Pterygial Cells via Inhibiting Chemokine (C-X-C Motif) Ligands in Microenvironment

Pterygium is a prevalent ocular surface condition characterized by its extension toward the cornea at the corneoscleral junction. The etiology and development of pterygium are not fully understood. The discovery of new biomarkers may facilitate early intervention and the prevention of postoperative recurrence. Kisspeptin and GPR54 expression in pterygium were investigated <i>in vivo</i> by qPCR, Western blotting (WB), and immunohistochemistry (IHC). Primary pterygial cells were treated with Kiss1 over-expression and GPR54 inhibitor and subsequently subjected to RNA sequencing. Signaling pathways were examined using WB and immunofluorescence (IF). The Kisspeptin/GPR54 system is down-regulated in pterygium. Ectopic over-expression of kisspeptin or GPR54 suppresses the cell growth of pterygial cells, accompanied by downregulation of chemokine signaling pathways (CXCL1, CXCL6 and CXCL12) and activation of the TGFβ, PI3K/Akt, p38 and ERK pathways as indicated by RNA-seq analysis. Furthermore, administration of the chemokines CXCL1, CXCL6 and CXCL12 significantly enhances the proliferation of pterygial cells. We reveal that kisspeptin system exerts an anti-pterygium effect, and a portion of chemokines induced by kisspeptin plays an essential role in pterygium growth.