Glyceraldehyde-derived advanced glycation end-products preferentially induce VEGF expression and reduce GDNF expression in human astrocytes

Miyajima, Hideaki; Osanai, Makoto; Chiba, Hideki; Nishikiori, Nami; Kojima, Takashi; Ohtsuka, Kenji; Sawada, Norimasa

doi:10.1016/j.bbrc.2005.03.001

Cited by 16 publications

(15 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our previous studies have demonstrated that GDNF is an important factor in regulating vascular permeability in vitro (12)(13)(14). Since it is possible that vascular permeability is determined by the balance between permeabilityinducing and -inhibiting factors, we therefore defined the antipermeability activity as the expression level of VEGF subtracted from that of GDNF in a given setting, where the cells treated with a vehicle were used as a control and defined as 100% in PCR analysis.…”

Section: Resultsmentioning

confidence: 99%

“…Our previous study demonstrated that GDNF secreted from glial cells was a critical player in regulating the vascular permeability of the BRB (12)(13)(14). To examine whether the gene expression alterations in glial cells induced by RAR␣ agonists modulated the barrier function of endothelial cells, we measured fluxes of radiolabeled molecules using [ 14 C]inulin in a bMVEC-B.…”

Section: Rar␣-induced Phenotypic Alteration Of Glial Cells Affects Enmentioning

confidence: 99%

“…To examine whether the gene expression alterations in glial cells induced by RAR␣ agonists modulated the barrier function of endothelial cells, we measured fluxes of radiolabeled molecules using [ 14 C]inulin in a bMVEC-B. This system contained primary microvascular cells derived from bovine brain tissue for the study of microvascular endothelial cell tight junctions and the transport of molecules across the blood-brain barrier, having a histological architecture similar to the BRB (1,(12)(13)(14). After verifying that the endothelial cells expressed GDNF receptor GFR␣1 (Fig.…”

Section: Rar␣-induced Phenotypic Alteration Of Glial Cells Affects Enmentioning

confidence: 99%

“…While glial cell line-derived neurotrophic factor (GDNF) was originally identified as a neurotrophic differentiation factor for dopaminergic neurons in the central nervous system and retina (10,11), we have proposed the novel idea that GDNF secreted from glial cells is a critical factor in regulating the vascular permeability of the BRB in a biological unit comprised of capillary endothelial cells and glial cells via modulation of the barrier function of tight junctions (12)(13)(14). In addition, we have also demonstrated that certain advanced glycation end products that are formed under hyperglycemic conditions increase the vascular permeability of the BRB in vitro, which is achieved by the induction of VEGF and reduction of GDNF expression from glial cells, suggesting that phenotypic alteration of glial cells in diabetes is responsible for the BRB breakdown (12)(13)(14).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Glial Cell–Derived Cytokines Attenuate the Breakdown of Vascular Integrity in Diabetic Retinopathy

et al. 2007

Self Cite

View full text Add to dashboard Cite

The blood-retinal barrier (BRB) is a biological unit comprised of specialized capillary endothelial cells firmly connected by intercellular tight junctions and endotheliumsurrounding glial cells. The BRB is essential for maintaining the retinal microenvironment and low permeability and is compromised in an early phase during the progression of diabetic retinopathy. Here, we demonstrate that retinoic acid receptor (RAR)␣ stimulants preferentially act on glial cells rather than endothelial cells, resulting in the enhanced expression of glial cell line-derived neurotrophic factor (GDNF) through recruitment of the RAR␣-driven trans-acting coactivator to the 5-flanking region of the gene promoter. Conversely, RAR␣ decreases expression of vascular endothelial growth factor (VEGF)/vascular permeability factor. These gene expression alterations causally limit vascular permeability by modulating the tight junction function of capillary endothelium in a paracrine manner in vitro. The phenotypic transformation of glial cells mediated by RAR␣ is sufficient for significant reductions of vascular leakage in the diabetic retina, suggesting that RAR␣ antagonizes the loss of tight junction integrity induced by diabetes. These findings reveal that glial cell-derived cytokines such as GDNF and VEGF regulate BRB function, implying that the glial cell can be a possible therapeutic target in diabetic retinopathy. Diabetes

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Rar␣-induced Phenotypic Alteration Of Glial Cells Affects Enmentioning

confidence: 99%

Section: Rar␣-induced Phenotypic Alteration Of Glial Cells Affects Enmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Glial Cell–Derived Cytokines Attenuate the Breakdown of Vascular Integrity in Diabetic Retinopathy

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…The expression of GDNF is also decreased in astrocytes by treatment with glyceraldehyde-derived advanced glycation endproducts (Miyajima et al, 2005), and this might have relevance in the context of the blood-brain barrier since GDNF reduces its permeability (Igarashi et al, 1999).…”

Section: Negative Regulation Of Gdnf Expressionmentioning

confidence: 99%