In vitro analyses of the anti-fibrotic effect of SPARC silencing in human Tenon's fibroblasts: comparisons with mitomycin C
| Autor: | Li-Fong Seet, Roseline Su, Tina T. Wong, Li Zhen Toh |
|---|---|
| Přispěvatelé: | School of Materials Science & Engineering |
| Rok vydání: | 2011 |
| Předmět: |
conjunctiva
Tenon Capsule Mitomycin Apoptosis Biology Real-Time Polymerase Chain Reaction Collagen Type I Cicatrix Transforming Growth Factor beta2 Fibrosis Cell Movement medicine In Situ Nick-End Labeling Matrix Metalloproteinase 14 Gene silencing Humans Osteonectin Gene Silencing RNA Small Interfering Fibroblast Cells Cultured Chemokine CCL2 Cell Proliferation mitomycin C Gene knockdown Wound Healing Mitomycin C Interleukin-8 fibrosis SPARC Cell Biology Original Articles Fibroblasts medicine.disease Fibronectins Fibronectin medicine.anatomical_structure glaucoma Matrix Metalloproteinase 9 Gene Knockdown Techniques Immunology Cancer research biology.protein Molecular Medicine Matrix Metalloproteinase 2 Wound healing |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 |
| Popis: | Failure of glaucoma filtration surgery (GFS) is commonly attributed to scarring at the surgical site. The human Tenon’s fibroblasts (HTFs) are considered the major cell type contributing to the fibrotic response. We previously showed that SPARC (secreted protein, acidic, rich in cysteine) knockout mice had improved surgical success in a murine model of GFS. To understand the mechanisms of SPARC deficiency in delaying subconjunctival fibrosis, we used the gene silencing approach to reduce SPARC expression in HTFs and examined parameters important for wound repair and fibrosis. Mitomycin C-treated HTFs were used for comparison. We demonstrate that SPARC-silenced HTFs showed normal proliferation and negligible cellular necrosis but were impaired in motility and collagen gel contraction. The expression of pro-fibrotic genes including collagen I, MMP-2, MMP-9, MMP-14, IL-8, MCP-1 and TGF-β2 were also reduced. Importantly, TGF-β2 failed to induce significant collagen I and fibronectin expressions in the SPARC-silenced HTFs. Together, these data demonstrate that SPARC knockdown in HTFs modulates fibroblast functions important for wound fibrosis and is therefore a promising strategy in the development of anti-scarring therapeutics. |
| Databáze: | OpenAIRE |
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