RGD Reference Report - Intraocular expression and release of high-mobility group box 1 protein in retinal detachment. - Rat Genome Database

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Intraocular expression and release of high-mobility group box 1 protein in retinal detachment.

Authors: Arimura, N  Ki-i, Y  Hashiguchi, T  Kawahara, K  Biswas, KK  Nakamura, M  Sonoda, Y  Yamakiri, K  Okubo, A  Sakamoto, T  Maruyama, I 
Citation: Arimura N, etal., Lab Invest. 2009 Mar;89(3):278-89. Epub 2009 Jan 12.
RGD ID: 2316760
Pubmed: PMID:19139725   (View Abstract at PubMed)
DOI: DOI:10.1038/labinvest.2008.165   (Journal Full-text)

High-mobility group box 1 (HMGB1) protein is a multifunctional protein, which is mainly present in the nucleus and is released extracellularly by dying cells and/or activated immune cells. Although extracellular HMGB1 is thought to be a typical danger signal of tissue damage and is implicated in diverse diseases, its relevance to ocular diseases is mostly unknown. To determine whether HMGB1 contributes to the pathogenesis of retinal detachment (RD), which involves photoreceptor degeneration, we investigated the expression and release of HMGB1 both in a retinal cell death induced by excessive oxidative stress in vitro and in a rat model of RD-induced photoreceptor degeneration in vivo. In addition, we assessed the vitreous concentrations of HMGB1 and monocyte chemoattractant protein 1 (MCP-1) in human eyes with RD. We also explored the chemotactic activity of recombinant HMGB1 in a human retinal pigment epithelial (RPE) cell line. The results show that the nuclear HMGB1 in the retinal cell is augmented by death stress and upregulation appears to be required for cell survival, whereas extracellular release of HMGB1 is evident not only in retinal cell death in vitro but also in the rat model of RD in vivo. Furthermore, the vitreous level of HMGB1 is significantly increased and is correlated with that of MCP-1 in human eyes with RD. Recombinant HMGB1 induced RPE cell migration through an extracellular signal-regulated kinase-dependent mechanism in vitro. Our findings suggest that HMGB1 is a crucial nuclear protein and is released as a danger signal of retinal tissue damage. Extracellular HMGB1 might be an important mediator in RD, potentially acting as a chemotactic factor for RPE cell migration that would lead to an ocular pathological wound-healing response.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
retinal detachment  IEP 2316760protein:increased expression:vitreous humor (human)RGD 
retinal detachment  ISOCCL2 (Homo sapiens)2316760; 2316760protein:increased expression:vitreous humor (human)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
chemotaxis  IDA 2316760 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccl2  (C-C motif chemokine ligand 2)
Hmgb1  (high mobility group box 1)

Genes (Mus musculus)
Ccl2  (C-C motif chemokine ligand 2)

Genes (Homo sapiens)
CCL2  (C-C motif chemokine ligand 2)

Objects referenced in this article
Gene CCL13 C-C motif chemokine ligand 13 Homo sapiens

Additional Information