Effects of the matricellular protein SPARC on human retinalpigment epithelial cell behavior

[摘要] Purpose: To determine the effects of the matricellular protein SPARC(Secreted Protein, Acidic and Rich in Cysteine) on human retinal pigmentepithelial (HRPE) cell behavior in vitro.Methods: Proliferation and migration assays were performed on HRPEcells exposed to various concentrations of SPARC. Additionally, HRPEcells were seeded on top of collagen matrices (a 2D model of the retinalscarring disorder known as proliferative vitreoretinopathy or PVR) andwere exposed to SPARC over a 7 day period. Changes in matrix contractionwere recorded.Results: HRPE cell proliferation was significantly inhibited at 1and 10 μg/ml SPARC (p<0.01). SPARC protein did not stimulate HRPEcell migration at any of the concentrations used. SPARC did notsignificantly affect fibronectin-induced HRPE cell migration at SPARCconcentrations up to 10 μg/ml. HRPE cell-seeded collagen matricesdemonstrated a significant inhibition of matrix contraction by 1 and 10μg/ml SPARC (t-test; p<0.02 and 0.001, respectively) compared tocontrols.Conclusions: SPARC protein has anti-proliferative effects on HRPEcells in vitro. In addition, SPARC appears to have an inhibitory effecton HRPE-mediated contraction of 2D collagen matrices. These results areconsistent with an important role for SPARC in modulating cell behaviorin vitro and may indicate a role for SPARC in modifying HRPE cellactivities during the development of PVR and other proliferative retinaldiseases.

[学科分类] 生物化学/生物物理