FGF-2- and TGF-β1-induced downregulation of lumican and keratocan in activated corneal keratocytes by JNK signaling pathway
| Autor: | Nirmala SundarRaj, Jian Chen, Julie Wong-Chong |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Lumican
genetic structures Keratan sulfate Corneal Stroma Down-Regulation Corneal Keratocytes Biology Fibroblast growth factor Collagen fibril organization Extracellular matrix Transforming Growth Factor beta1 chemistry.chemical_compound Animals Mitogen-Activated Protein Kinase 9 Mitogen-Activated Protein Kinase 8 Eye Proteins Cells Cultured Anthracenes Wound Healing Articles eye diseases Cell biology carbohydrates (lipids) Phenotype chemistry Biochemistry Chondroitin Sulfate Proteoglycans Keratan Sulfate Fibroblast Growth Factor 2 Proteoglycans sense organs Rabbits Wound healing Keratocan Myofibroblast Signal Transduction |
| Zdroj: | Investigative ophthalmologyvisual science. 52(12) |
| ISSN: | 1552-5783 |
| Popis: | The cornea is a transparent avascular refractive structure consisting of three tissue layers, epithelium, stroma, and endothelium. A well-organized extracellular matrix (ECM) containing densely packed and regularly spaced thin collagen fibrils of uniform diameter, is largely responsible for transparency in the corneal stroma.1–3 Keratan sulfate proteoglycans (KSPGs) in the stromal ECM play a critical role in the development and maintenance of corneal transparency. Keratocan and lumican, the major KSPGs in the corneal stroma, regulate both fibril diameter and interfibrillar spacing as evident from the phenotype of lumican and keratocan knockout mice.4–9 Keratocan knockout mice have a thinner corneal stroma with irregular collagen fibril organization compared with the normal mice,8 and lumican knockout mice have increased collagen fibril diameter and develop opaque corneas.4,5 Corneal stromal cells (keratocytes), which synthesize keratocan and lumican during development, become quiescent in a fully-developed cornea. However, after an injury to the cornea, growth factors and cytokines originating from corneal epithelial cells, inflammatory cells, and tear fluid activate the keratocytes to fibroblast or myofibroblast phenotypes (reviews, see Refs. 10–14). Keratocan and lumican synthesis is downregulated in the activated keratocytes during wound healing.15–18 KSPG expression is also downregulated in vitro when cultured keratocytes are activated with growth factors including FGF-2 and TGF-β1.19–23 Therefore, an in vitro model of keratocyte activation is useful to study the signaling mechanisms that downregulate the expression of KSPGs. We had previously demonstrated that activation of the small GTPase Rho and its downstream target Rho kinase (ROCK) regulate several undesirable phenotypic changes including the downregulation of KSPGs in the activated keratocytes.23 Jun N-terminal kinase (JNK), a member of the mitogen activated protein kinase (MAPK) family, has been shown to mediate some of the Rho/ROCK regulated events.24–26 The present study was designed to investigate whether JNK activation is responsible for the observed TGF-β1– and FGF-2–induced downregulation of KSPGs in activated keratocytes. |
| Databáze: | OpenAIRE |
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