Expression of Acute-Phase Response Proteins in Retinal Müller Cells in Diabetes

Gerhardinger, Chiara; Costa, Montserrat Biarne ́s; Coulombe, Mary C.; Tóth, Ildikó; Hoehn, Todd; Grosu, Paul

doi:10.1167/iovs.04-0860

Cited by 236 publications

(225 citation statements)

References 43 publications

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“…Studies of retinal VEGF mRNA expression in STZ-induced diabetic rats have produced conflicting results, with VEGF mRNA concentrations reported to be increased [34,53,54], decreased [55,56] or unchanged [57] in diabetic rats compared with levels in control rats. The present findings show that, following diabetes, there is a higher phosphorylation of the HuR protein by PKCβ resulting in the activation of HuR itself that then targets VEGF mRNA, finally leading to an increased amount of the correspondent VEGF protein (Fig.…”

Section: Discussionmentioning

confidence: 99%

The PKCβ/HuR/VEGF pathway in diabetic retinopathy

Amadio¹,

Bucolo²,

Leggio³

et al. 2010

Biochemical Pharmacology

100

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Section: Discussionmentioning

confidence: 99%

The PKCβ/HuR/VEGF pathway in diabetic retinopathy

Amadio¹,

Bucolo²,

Leggio³

et al. 2010

Biochemical Pharmacology

100

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“…Pro-inflammatory cytokines such as IL-1β play a crucial role in the pathogenesis of both PDR and DMO [19][20][21][22]. Apart from its intrinsic deleterious effect, IL-1β has been shown to stimulate several pro-inflammatory cytokines such as IL-6, IL-8 and monocyte chemotactic protein 1 (MCP-1) [26,27], which, in turn, have also been involved in both PDR and DMO [28][29][30].…”

Section: Discussionmentioning

confidence: 99%

“…In fact, treatment of RPE cells with either serum, interferon-γ, tumour necrosis factor-α, hepatocyte growth factor (HGF), IL-1β or placental growth factor-1 (PLGF-1) increases permeability and alters the levels or content of tight junction molecules [14][15][16][17][18]. As IL-1β plays an essential role in the development of DR [19][20][21][22], we decided to use this cytokine to provoke the breakdown of the RPE cell monolayer and to test the potential preventive effects of fenofibrate.…”

Section: Introductionmentioning

confidence: 99%

Fenofibric acid prevents retinal pigment epithelium disruption induced by interleukin-1β by suppressing AMP-activated protein kinase (AMPK) activation

et al. 2011

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Aims/hypothesis The mechanisms involved in the beneficial effects of fenofibrate on the development and progression of diabetic macular oedema (DMO) remain to be elucidated. To shed light on this issue we have explored the effect of fenofibric acid on the barrier function of human retinal pigment epithelium (RPE) cells. Methods ARPE-19 cells (a human RPE line) were cultured for 18 days under standard conditions and under conditions leading to the disruption of the monolayer (D-glucose, 25 mmol/l, with IL-1β, 10 ng/ml, added at days 16 and 17). Fenofibric acid, 25 μmol/l and 100 μmol/l, was added on the last 3 days of the experiment (one application/day). RPE cell permeability was evaluated by measuring apicalbasolateral movements of FITC-dextran (40 kDa). The production of tight junction proteins and AMP-activated protein kinase (AMPK) phosphorylation was assessed by western blot. Immunohistochemical studies of tight junction proteins and small interfering RNA transfection to AMPK were also performed in ARPE-19 monolayers. Results Treatment of ARPE-19 cells with fenofibric acid significantly reduced the increment of permeability and the breakdown of the ARPE-19 cell monolayer induced by Dglucose, 25 mmol/l, and IL-1β, 10 ng/ml, in a dose-dependent manner. This effect was unrelated to changes in the content of tight junction proteins. Fenofibric acid prevented the activation of AMPK induced by IL-1β and the hyperpermeability induced by IL-1β was blocked by silencing AMPK. Conclusions/interpretation Disruption of RPE induced by IL-1β is prevented by fenofibric acid through its ability to suppress AMPK activation. This mechanism could be involved in the beneficial effects of fenofibrate on DMO development.

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“…Retinal Müller glial cells are known to express these proteins [55], and acutephase response is believed to contribute to defensive or adaptive capabilities, although the excessive overproduction of acute-phase proteins may result in tissue damage [54]. Moreover, ceruloplasmin has been found to induce endothelial dysfunction, and transferrin was found to be proangiogenic [56,57].…”

Section: Pathogenic Implications Of Identified Proteins On Pdrmentioning

confidence: 99%

Profiling of vitreous proteomes from proliferative diabetic retinopathy and nondiabetic patients

Kim

et al. 2007

Proteomics

133

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Diabetes can lead to serious microvascular complications like proliferative diabetic retinopathy (PDR), which is the leading cause of blindness in adults. The proteomic changes that occur during PDR cannot be measured in the human retina for ethical reasons, but could be reflected by proteomic changes in vitreous humor. Thus, we considered that comparisons between the proteome profiles of the vitreous humors of PDR and nondiabetic controls could lead to the discovery of novel pathogenic proteins and clinical biomarkers. In this study, the authors used several proteomic methods to comprehensively examine vitreous humor proteomes of PDR patients and nondiabetic controls. These methods included immunoaffinity subtraction (IS)/2-DE/ MALDI-MS, nano-LC-MALDI-MS/MS, and nano-LC-ESI-MS/MS. The identified proteins were subjected to the Trans-Proteomic Pipeline validation process. Resultantly, 531 proteins were identified, i.e., 415 and 346 proteins were identified in PDR and nondiabetic control vitreous humor samples, respectively, and of these 531 proteins, 240 were identified for the first time in this study. The PDR vitreous proteome was also found to contain many proteins possibly involved in the pathogenesis of PDR. The proteins described provide the most comprehensive proteome listing in the vitreous humor samples of PDR and nondiabetic control patients.

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Expression of Acute-Phase Response Proteins in Retinal Müller Cells in Diabetes

Cited by 236 publications

References 43 publications

The PKCβ/HuR/VEGF pathway in diabetic retinopathy

The PKCβ/HuR/VEGF pathway in diabetic retinopathy

Fenofibric acid prevents retinal pigment epithelium disruption induced by interleukin-1β by suppressing AMP-activated protein kinase (AMPK) activation

Profiling of vitreous proteomes from proliferative diabetic retinopathy and nondiabetic patients

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