Abstract
Sphingosine 1 phosphate (S1P) is a bioactive lipid that regulates cellular activity, including proliferation, cytoskeletal organization, migration, and fibrosis. In this study, the potential relevance of S1P–Rho signaling in pterygium formation and the effects of ultraviolet (UV) irradiation on activation of the S1P/S1P receptor axis and fibrotic responses were investigated in vitro. Expressions of the S1P2, S1P4, and S1P5 receptors were significantly higher in pterygium tissue than in normal conjunctiva, and the concentration of S1P was significantly elevated in the lysate of normal conjunctival fibroblast cell (NCFC) irradiated with UV (UV-NCFCs). RhoA activity was significantly upregulated in pterygium fibroblast cells (PFCs) and UV-NCFCs, and myosin phosphatase–Rho interacting protein (MRIP) was upregulated, and myosin phosphatase target subunit 1 (MYPT1) was downregulated in PFCs. Fibrogenic changes were significantly upregulated in both PFCs and UV-NCFCs compared to NCFCs. We found that the activation of the S1P receptor–Rho cascade was observed in pterygium tissue. Additionally, in vitro examination showed S1P–rho activation and fibrogenic changes in PFCs and UV-NCFCs. S1P elevation and the resulting upregulation of the downstream Rho signaling pathway may be important in pterygium formation; this pathway offers a potential therapeutic target for suppressing pterygium generation.
Highlights
Pterygium is defined as a condition with the invasion of wing-shaped chronic proliferative fibrovascular tissue into normal corneal epithelium
We investigated the involvement of the Sphingosine 1 phosphate (S1P)–RhoA pathway in pterygium tissue, compared to normal conjunctiva, and whether UV irradiation modulates the expression of this pathway and fibrotic properties in cultured pterygium fibroblast cells and normal conjunctival cells
As SphK2 expression was upregulated in pterygium fibroblast cells (PFCs) and UV-normal conjunctival fibroblast cell (NCFC) compared to NCFCs, we pe2rf.4oA.rmEsxeSpdprehismKsim2oneuoxnfpoSrc1eysPtsoiaocnhndewSm1aiPsst2ruRyp(arEegDgauiGnl-as5tt)eSdi1nPiNnaCPnFFdCCSss1, PaPn2FRdCs(U,EaVDn-GdN-UC5V)Fi-CnNsNCcFCoCmFsCpsa,rPedFCtos,NanCdFCUsV,wNeCnFCexst
Summary
Pterygium is defined as a condition with the invasion of wing-shaped chronic proliferative fibrovascular tissue into normal corneal epithelium. UV radiation is an environmental causative factor [2,3,4,5,6,7,8]; chronic UV irradiation causes pathophysiological changes in limbal basal stem cells and conjunctival fibroblasts [2,9,10]. Along with the change in the characteristics of limbal stem cells and fibroblasts, kinases, several pro-inflammatory cytokines, and growth factors are upregulated in pterygium tissue. We investigated the involvement of the S1P–RhoA pathway in pterygium tissue, compared to normal conjunctiva, and whether UV irradiation modulates the expression of this pathway and fibrotic properties in cultured pterygium fibroblast cells and normal conjunctival cells. Our results establish a correlation between UV light exposure and S1P–RhoA pathway involvement, providing insight into the pathogenesis of pterygium
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