445회 The initial switch of the FGF-2-mediated corneal fibrosis causing…

445회 

연사:  이정구 박사

제목 : IL-1b: The initial switch of the FGF-2-mediated corneal fibrosis causing blindness in vitro and in vivo system

Abstract 

  Such characteristic behavior of cell proliferation dictates the regenerative (physiological) wound healing process occurring in the corneal endothelium. On the other hand, in the non-regenerative (pathological) wound healing process, corneal fibrosis represents a significant pathophysiological problem - one that causes blindness by physically blocking light transmittance. One clinical example of corneal fibrosis observed in corneal endothelium is the development of a retrocorneal fibrous membrane (RCFM) in Descemet’s membrane. In such RCFM, CECs are converted to fibroblast-like cells: the characteristic contact-inhibited monolayer of CECs is lost, resulting in the development of multi-layers of fibroblast-like cells. These morphologically altered cells simultaneously resume their proliferation ability. Corenal fibrosis in the corneal endothelium leads to blindness. Endothelial mesenchymal transformation (EMT) observed in corneal fibrosis demonstrated that IL-1β is the initial switch that upregulates FGF-2 production and that the IL-1β-induced FGF-2 is the direct mediator of EMT in corneal endothelial cells (CECs). Using both in vivo and in vitro models, we determined whether IL-1β employs PI 3-kinase during induction of FGF-2, and we further identified the downstream signaling of PI 3-kinase pathway. Brief stimulation of cells with IL-1β activated PI 3-kinase and p38: specific inhibitors for PI 3-kinase (LY294002) and p38 (SB203580) blocked production of FGF-2 mediated IL-1β. Similarly, transcorneal freezing caused FGF-2 production in corneal endothelium, and topical treatment with either inhibitor on the cornea after cryo-treatment reduced FGF-2 levels, IL-1β activates nuclear factor kB while inducing production of FGF-2, through PI 3-kinase and p38 pathways. These data suggest that PI 3-kinase pathway is the major signal transduction in the respective events during pathological wound healing: injury-mediated inflammatory response (IL-1β-mediated FGF-2 production).