High-Mobility Group Box-1 Modulates the Expression of Inflammatory and Angiogenic Signaling Pathways in Diabetic Retina

El-Asrar, A M Abu; Mohammad, Ghulam; Nawaz, Mohd Imtiaz; Mm, Siddiquei

doi:10.3109/02713683.2014.982829

Cited by 32 publications

(31 citation statements)

References 63 publications

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“…In previous studies, we demonstrated that constant GA intake attenuated diabetes-induced upregulation of HMGB1 in the retinas of rats [14,15] . Western blot analysis was used to assess the effect of GA on diabetes-induced upregulation of STAT-3.…”

Section: Ga Attenuates Diabetes-induced Upregulation Of Pstat-3 Exprementioning

confidence: 83%

“…Moreover, our recent study showed a positive correlation between the vitreous fluid levels of HMGB1 and the levels of the protein oxidation marker protein carbonyl content and suggested the presence of a mechanis- tic link between HMGB1 and oxidative stress in the pathogenesis of PDR [16] . Furthermore, a great deal of evidence has indicated the critical importance of HMGB1 in mediating inflammation, breakdown of the BRB, oxidative stress, apoptosis and neuropathy in the diabetic retina [14][15][16][17][18][19] . However, its downstream signal transduction pathways in the pathogenesis of DR are still not well understood.…”

Section: Discussionmentioning

confidence: 99%

“…In a previous study we demonstrated that treatment with recombinant HMGB1 protein induced significant upregulation of the inflammatory biomarkers interleukin-1β, ICAM-1, and VEGF [14,15] . To determine the effect of recombinant HMGB1 protein on the expression of pSTAT-3 in retinal Müller cells, we treated the starved retinal Müller cells with 100 ng/ml of recombinant HMGB1 for 24 h, and then whole cell lysates (n = 12) were examined for pSTAT-3 expression.…”

Section: Hmgb1 Induces Nuclear Translocation Of Pstat-3 In Retinal Mümentioning

confidence: 91%

“…Recent studies demonstrated that diabetes-or highglucose-induced activation of STAT-3 regulates the inflammatory response, the expression of VEGF and ICAM-1 and the integrity of the BRB in the retina [24][25][26] . We have recently shown that HMGB1 regulates the expression of VEGF, ICAM-1 and integrity of the BRB in the diabetic retina [14,15] .…”

mentioning

confidence: 99%

“…Furthermore, we demonstrated that diabetes induced significant upregulation of the expression of HMGB1, RAGE, activated extracellular signal-regulated kinase 1 and 2 (ERK1/2) and activated nuclear factor-κB in the retinas of rats and mice and that intravitreal administration of HMGB1 in normal rats mimics the effect of diabetes [14] . Recently, a great deal of evidence has indicated that the extracellular HMGB1-induced altered cell signaling pathways in the retina play a pivotal role in the pathogenesis of DR [15][16][17][18][19] .…”

mentioning

confidence: 99%

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High-Mobility Group Box-1 Protein Mediates the Regulation of Signal Transducer and Activator of Transcription-3 in the Diabetic Retina and in Human Retinal Müller Cells

et al. 2016

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Purpose: The expression of high-mobility group box-1 (HMGB1) and signal transducer and activator of transcription-3 (STAT-3) is upregulated in the diabetic retina. We hypothesized that the activation of STAT-3 is under the control of HMGB1. Methods: Retinas from 1-month-old diabetic rats and from normal rats intravitreally injected with HMGB1 and human retinal Müller glial cells (MIO-M1) stimulated with HMGB1 or high glucose were studied by Western blot analysis and immunofluorescence. We also studied the effect of the HMGB1 inhibitor glycyrrhizin (GA) on high-glucose-induced pSTAT-3 nuclear translocation and upregulation in Müller cells and on pSTAT-3 expression in the retinas of diabetic rats (n = 7-10 in each group). In addition, we studied the effect of STAT-3 inhibitor on the HMGB1-induced induction of vascular endothelial growth factor (VEGF) by Müller cells and human retinal microvascular endothelial cell (HRMEC) migration. Results: Treatment of retinal Müller cells with recombinant HMGB1 induced nuclear translocation of pSTAT-3 but did not alter pSTAT-3 expression. High glucose induced a significant upregulation of HMGB1 and pSTAT-3 upregulation and nuclear translocation in retinal Müller cells. GA co-treatment normalized the high-glucose-induced upregulation of HMGB1 and pSTAT-3 upregulation and nuclear translocation in Müller cells. Intravitreal administration of HMGB1 in normal and diabetic rats upregulated pSTAT-3 expression in the retina. GA attenuated the diabetes-induced upregulation of pSTAT-3 in the retina. The STAT-3 inhibitor attenuated HMGB1-induced VEGF upregulation by Müller cells and HRMEC migration. Conclusions: The results suggest a role for HMGB1 in the modulation of STAT-3 expression in the diabetic retina.

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Section: Ga Attenuates Diabetes-induced Upregulation Of Pstat-3 Exprementioning

confidence: 83%