Role of the Proteasome in TGF-β Signaling in Lens Epithelial Cells

Hosler, Matthew R.; Wang-Su, Shuh-Tuan; Wagner, B.J.

doi:10.1167/iovs.05-0650

Cited by 22 publications

(18 citation statements)

References 57 publications

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“…The 26S proteasome is a ~2500 kDa complex consisting of one 20S core particle (CP) and two 19S regulatory particles (RPs) (Murata et al, 2009). Previous studies using in vitro cultures showed that the UPS is required for the proliferation of lens epithelial cells (Guo et al, 2006), mitochondrial degradation during lens fiber differentiation (Zandy and Bassnett, 2007), TGF-mediated lens fiber cell differentiation (Wu et al, 2007) and posterior capsular opacification (Hosler et al, 2006). It was reported that the UPS cooperates with a chaperone system to control protein quality (Bian et al, 2008;Bornheim et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

The ubiquitin proteasome system is required for cell proliferation of the lens epithelium and for differentiation of lens fiber cells in zebrafish

et al. 2010

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SUMMARYIn the developing vertebrate lens, epithelial cells differentiate into fiber cells, which are elongated and flat in shape and form a multilayered lens fiber core. In this study, we identified the zebrafish volvox (vov) mutant, which shows defects in lens fiber differentiation. In the vov mutant, lens epithelial cells fail to proliferate properly. Furthermore, differentiating lens fiber cells do not fully elongate, and the shape and position of lens fiber nuclei are affected. We found that the vov mutant gene encodes Psmd6, the subunit of the 26S proteasome. The proteasome regulates diverse cellular functions by degrading polyubiquitylated proteins. Polyubiquitylated proteins accumulate in the vov mutant. Furthermore, polyubiquitylation is active in nuclei of differentiating lens fiber cells, suggesting roles of the proteasome in lens fiber differentiation. We found that an E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) is involved in lens defects in the vov mutant. These data suggest that the ubiquitin proteasome system is required for cell proliferation of lens epithelium and for the differentiation of lens fiber cells in zebrafish.

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Section: Introductionmentioning

confidence: 99%

The ubiquitin proteasome system is required for cell proliferation of the lens epithelium and for differentiation of lens fiber cells in zebrafish

et al. 2010

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“…The SV-40 virus immortalized human lens epithelial cell line HLE B-3 was selected for use in the coculture model. Although differences between the proteomes of native lens epithelial cells and HLE B-3 have been investigated, namely the absence of crystalline expression in HLE B-3, 56 the cell line continues to be used extensively to study signaling pathways and mechanisms in PCO, 12,15,16,42,43,57 and capsular biocompatibility with IOL materials. 58,59 Our objective was to examine the uveal biocompatibility of PMMA and pHEMA IOL materials by quantifying cellular activation.…”

Section: Discussionmentioning

confidence: 99%

“…5 Chung et al 42 showed that treatment with TGF-b 1 induced fibronectin expression in HLE B-3 cells, while Hosler et al 16 showed that treatment with TGF-b 2 induced fibronectin gene activation in HLE B-3 and primary cells. Choi et al 12 observed that TGF-b 1 treatment repressed E-cadherin expression in HLE B-3 cells, while a similar study by Yao et al 82 observed the same finding but in alveolar epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…10 The primary chemical mediator of PCO has been demonstrated both in vitro and in vivo to be the cytokine transforming growth factor beta (TGF-b). [11][12][13][14][15][16][17][18] Additionally, members of the matrix metalloproteinase (MMP) family of zinc-dependent endoproteinasesspecifically MMP-2 and MMP-9-have been shown to play a regulatory role in the formation of PCO. 5 Interestingly, these three mediators are secretory products of macrophages, who play a crucial role in regulating inflammatory processes and the wound-healing response to biomaterials.…”

Section: Introductionmentioning

confidence: 99%

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Coculture with intraocular lens material-activated macrophages induces an inflammatory phenotype in lens epithelial cells

et al. 2014

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Cataracts are the leading cause of blindness worldwide, requiring surgical implantation of an intraocular lens. Despite evidence of leukocyte ingress into the postoperative lens, few studies have investigated the leukocyte response to intraocular lens materials. A novel coculture model was developed to examine macrophage activation by hydrophilic acrylic (poly(2-hydroxyethyl methacrylate)) and hydrophobic acrylic (polymethylmethacrylate) commercial intraocular lens. The human monocytic cell line THP-1 was differentiated into macrophages and cocultured with human lens epithelial cell line (HLE-B3) with or without an intraocular lens for one, two, four, or six days. Using flow cytometry and confocal microscopy, expression of the macrophage activation marker CD54 (intercellular adhesion molecule-1) and production of reactive oxygen species via the fluorogenic probe 2',7'-dichlorodihydrofluorescein diacetate were examined in macrophages. α-Smooth muscle actin, a transdifferentiation marker, was characterized in lens epithelial cells. The poly(2-hydroxyethyl methacrylate) intraocular lens prevented adhesion but induced significant macrophage activation (p < 0.03) versus control (no intraocular lens), while the polymethylmethacrylate intraocular lens enabled adhesion and multinucleated fusion, but induced no significant activation. Coculture with either intraocular lens increased reactive oxygen species production in macrophages after one day (p < 0.03) and increased expression of α-smooth muscle actin in HLE B-3 after six days, although only poly(2-hydroxyethyl methacrylate) induced a significant difference versus control (p < 0.01). Our results imply that-contrary to prior uveal biocompatibility understanding-macrophage adherence is not necessary for a strong inflammatory response to an intraocular lens, with hydrophilic surfaces inducing higher activation than hydrophobic surfaces. These findings provide a new method of inquiry into uveal biocompatibility, specifically through the quantification of cell-surface markers of leukocyte activation.

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“…It has also been shown that the proteasome can mediate ASC cataract [84,85]. The HLE B-3 cell line and primary cultured human lens cells respond similarly to TGF-β treatments by activating cataract-related gene expression and this response was blocked by inhibiting the proteasome, suggesting that proteasome inhibitors could be candidates for blocking development of PCO.…”

Section: Proteases In Pcomentioning

confidence: 99%

Role of proteases in the development and diseases of the lens

Wride

2007

Expert Review of Ophthalmology

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Proteases have important roles in development and in disease. Here, the recent literature pertaining to the role of proteases in lens development (including lens fiber cell organelle loss) and cataract progression is reviewed. Families of proteases reviewed include caspases, calpains, cathepsins, the ubiquitin proteasome pathway and matrix metalloproteases. Proteases are also considered as potential targets for the pharmaceutical treatment for cataract and complications of cataract surgery, such as posterior capsule opacification. The development and use of such drugs is dependent upon gaining further insights into the roles of proteases in lens development, maturation, aging and cataract. Fruitful avenues for future research in this area are also identified.

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Role of the Proteasome in TGF-β Signaling in Lens Epithelial Cells

Cited by 22 publications

References 57 publications

The ubiquitin proteasome system is required for cell proliferation of the lens epithelium and for differentiation of lens fiber cells in zebrafish

The ubiquitin proteasome system is required for cell proliferation of the lens epithelium and for differentiation of lens fiber cells in zebrafish

Coculture with intraocular lens material-activated macrophages induces an inflammatory phenotype in lens epithelial cells

Role of proteases in the development and diseases of the lens

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