SPARC is expressed in scars of the Tenon’s capsule and mediates scarring properties of human Tenon’s fibroblasts in vitro

[摘要] Purpose: To investigate the expressionof the matricellular protein SPARC (secreted acidic cysteine-richglycoprotein) in scarred human Tenon’s capsule and in cultured humanTenon’s fibroblasts (HTF), and to analyze the influence of SPARC oncell proliferation and collagen matrix contraction in vitro. Methods: Human Tenon's capsule scarsobtained from surgical revisions after filtration surgery were analyzedfor SPARC expression by immunohistochemistry. In cultured HTF cells,SPARC expression was assessed by northern and western blot analysesafter incubation with transforming growth factor (TGF)-β1 and TGF-β2.Cell proliferation was determined by bromodeoxyuridine (BrdU)–labelingand HTF cells-mediated collagen matrix contraction by morphometricmeasurements of three-dimensional collagen lattices after treatmentwith SPARC and/or TGF-β1. Results: In scarred human Tenon’scapsule specimens, an increased expression of SPARC was mainlylocalized to the extracellular matrix and to blood vessel walls ascompared to healthy control Tenon’s capsule. In cultured HTF cells,treatment with TGF-β1 more than TGF-β2 induced the expression of SPARCboth on the mRNA and protein level. Incubation of HTF cells with SPARCresulted in an increase in collagen matrix contraction and cellproliferation. Moreover, a combined incubation of SPARC and TGF-β1stimulated HTF cell proliferation significantly over the levels thatwere observed after single treatment. Conclusions: Our data provide evidencethat SPARC contributes to excessive wound healing and scar formation inhuman Tenon’s capsules after filtration surgery and may thus representa novel target for anti-fibrotic strategies.

[学科分类] 生物化学/生物物理