Advanced glycation end products increase endothelial permeability through the RAGE/Rho signaling pathway

Hirose, Akiko; Tanikawa, Takahisa; Mori, Hiroko; Okada, Yosuke; Tanaka, Yoshiya

doi:10.1016/j.febslet.2009.11.082

Cited by 110 publications

(80 citation statements)

References 17 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…When these high doses of alendronate are co-incubated with AGEs-BSA, the morphological and cytoskeletal disruption of osteoblasts are significantly greater than that of each agent on its own, suggesting the involvement of independent and/or additive mechanisms. For instance, AGEs could possibly be interfering with the integrinmediated recognition of (and attachment to) the ECM, and possibly could also induce activation of RAGE (receptor for AGEs) in a mechanism involving RhoA that generates intercellular gaps, prominent stress fibers and cell contraction, as described by other authors for endothelial cells (Hirose et al, 2010). On the other hand, highdose alendronate can affect the actin cytoskeleton and formation of focal adhesions through its actions on the geranylgeranylation of RhoA and, potentially, through these effects could influence the remodeling of bone (Kazmers et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Morphological changes induced by advanced glycation endproducts in osteoblastic cells: Effects of co-incubation with alendronate

et al. 2013

View full text Add to dashboard Cite

a b s t r a c tAdvanced glycation endproducts (AGEs) accumulate with age in various tissues, and are further increased in patients with Diabetes mellitus, in which they are believed to contribute to the development and progression of chronic complications that include a decrease in bone quality. Bisphosphonates are antiosteoporotic drugs that have been used for the treatment of patients with diabetic bone alterations, although with contradictory results. In the present study, we have evaluated the in vitro alterations on osteoblastic morphology by environmental scanning electron microscopy, in actin cytoskeleton and apoptosis induced by AGEs, as well as the modulation of these effects by alendronate (an N-containing bisphosphonate). Our present results provide evidence for disruption induced by AGEs of the osteoblastic actin cytoskeleton (geodesic domes) and significant alterations in cell morphology with a decrease in cellsubstratum interactions leading to an increase in apoptosis of osteoblasts and a decrease in osteoblastic proliferation. High concentrations of alendronate (10 −5 M, such as could be expected in an osteoclastic lacuna) further increase osteoblastic morphological and cytoskeletal alterations. However, low doses of alendronate (10 −8 M, compatible with extracellular fluid levels to which an osteoblast could be exposed for most of its life cycle) do not affect cell morphology, and in addition are able to prevent AGEs-induced alterations and consequently apoptosis of osteoblasts.

show abstract

Section: Discussionmentioning

confidence: 99%

Morphological changes induced by advanced glycation endproducts in osteoblastic cells: Effects of co-incubation with alendronate

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Activation of the Nrf2 pathway attenuates HG-mediated high glucose-induced hyperpermeability by attenuating ROS production [8,26]. High glucose, ROS, and the hexosamine pathway in vascular and renal cells have been demonstrated to activate the RhoA/ROCK signaling pathway [15,16]. Rutin herein prevented HG-induced hyperpermeability, and junction protein defects, activation of the RhoA/ROCK signaling pathway, and ROS were significantly abolished with the knockdown of Nrf2.…”

mentioning

confidence: 97%

“…Activity of the RhoA/ROCK pathway is enhanced in vascular and renal cells in various types of kidney disorders. The factors involved in diabetes mellitus, such as high glucose, ROS, and the hexosamine pathway in vascular and renal cells, can activate the RhoA/ROCK signaling pathway [15,16]. As a polyphenolic flavonoid, rutin has beneficial effects on renal damage by reducing oxidative stress [17,18] with anticancer and anti-inflammatory activities as well.…”

mentioning

confidence: 99%

Rutin Prevents High Glucose-Induced Renal Glomerular Endothelial Hyperpermeability by Inhibiting the ROS/Rhoa/ROCK Signaling Pathway

et al. 2016

View full text Add to dashboard Cite

Diabetic nephropathy is a progressive kidney disease caused by damage to the capillaries in the glomeruli. Endothelial dysfunction is an early sign of diabetic cardiovascular disease and may contribute to progressive diabetic nephropathy. Hyperglycemia-induced endothelial hyperpermeability is crucial to diabetic nephropathy. Rutin has beneficial effects on diabetic nephropathy, but the exact mechanisms of its protective effect remain elusive. The aim of this study was to assess the role of pretreatment with rutin in an in vitro model of hyperglycemia-induced barrier dysfunction in human renal glomerular endothelial cells. Human renal glomerular endothelial cells were exposed to rutin and/or hyperglycemia for 24?h. Hyperglycemia increased permeability and decreased the junction protein occludin in the cell-cell junction area and the total expression in human renal glomerular endothelial cells, whereas rutin treatment significantly corrected these abnormalities. Furthermore, hyperglycemia-induced activation of RhoA/ROCK was reversed by treatment with rutin or the knockdown of ROCK2. Interestingly, rutin prevented hyperglycemia-induced hyperpermeability, and dysfunction of the tight junction, a high level of reactive oxygen species, and activation of RhoA/ROCK were significantly abolished with the knockdown of Nrf2. In conclusion, rutin significantly prevented hyperglycemia-disrupted renal endothelial barrier function by inhibiting the RhoA/ROCK signaling pathway through decreasing reactive oxygen species, which was mediated by the activation of Nrf2. Our results may explain, at least in part, some beneficial effects of rutin that may be applicable to the treatment of vascular disorders in diabetic nephropathy.

show abstract

“…75). In vascular cells, this interaction results in the activation of a number of intracellular pathways, including PKC/Rho (16,17,76). The prototype therapeutic agent aminoguanidine is known to prevent AGE formation by reacting with derivatives of early glycation products, such as 3-deoxyg-lucosone (reviewed in Ref.…”

Section: No Diabetesmentioning

confidence: 99%

Elevated Glucose Levels Promote Contractile and Cytoskeletal Gene Expression in Vascular Smooth Muscle via Rho/Protein Kinase C and Actin Polymerization

Hien¹,

Turczyńska²,

Dahan³

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Both type 1 and type 2 diabetes are associated with increased risk of cardiovascular disease. This is in part attributed to the effects of hyperglycemia on vascular endothelial and smooth muscle cells, but the underlying mechanisms are not fully understood. In diabetic animal models, hyperglycemia results in hypercontractility of vascular smooth muscle possibly due to increased activation of Rho-kinase. The aim of the present study was to investigate the regulation of contractile smooth muscle markers by glucose and to determine the signaling pathways that are activated by hyperglycemia in smooth muscle cells. Microarray, quantitative PCR, and Western blot analyses revealed that both mRNA and protein expression of contractile smooth muscle markers were increased in isolated smooth muscle cells cultured under high compared with low glucose conditions. This effect was also observed in hyperglycemic Akita mice and in diabetic patients. Elevated glucose activated the protein kinase C and Rho/Rho-kinase signaling pathways and stimulated actin polymerization. Glucose-induced expression of contractile smooth muscle markers in cultured cells could be partially or completely repressed by inhibitors of advanced glycation end products, L-type calcium channels, protein kinase C, Rho-kinase, actin polymerization, and myocardin-related transcription factors. Furthermore, genetic ablation of the miR-143/145 cluster prevented the effects of glucose on smooth muscle marker expression. In conclusion, these data demonstrate a possible link between hyperglycemia and vascular disease states associated with smooth muscle contractility.Diabetes confers a 2-4-fold excess risk for a wide range of cardiovascular diseases, including macrovascular complications leading to coronary heart disease and ischemic stroke, as well as microvascular diseases, such as nephropathy and retinopathy (1, 2). Based on current trends, the rising incidence of diabetes (expected to reach 333 million people worldwide by 2025) will undoubtedly equate to increased cardiovascular mortality. Chronic hyperglycemia has long been recognized as an independent risk factor for cardiovascular disease (3, 4). Importantly, the progressive relationship between glucose levels and cardiovascular risk extends below the threshold for diabetes diagnosis (fasting plasma glucose Ն7.0 mmol/liter or 2-h plasma glucose Ն11.1 mmol/liter (2, 3)), and more recently, even transient hyper-and hypoglycemia have emerged as important determinants of cardiovascular disease (5). Despite the vast clinical and epidemiological experience linking blood glucose and poor glucose control to the development and progression of cardiovascular disease, the underlying molecular mechanisms leading to vascular dysfunction and disease are poorly understood (6).It has been well established that hyperglycemia results in vascular hyperreactivity in diabetic patients (7) and animal models (8 -10). Part of this effect may be attributed to a decrease in nitric oxide (NO) bioavailability as well as a reduced respon...

show abstract

Advanced glycation end products increase endothelial permeability through the RAGE/Rho signaling pathway

Cited by 110 publications

References 17 publications

Morphological changes induced by advanced glycation endproducts in osteoblastic cells: Effects of co-incubation with alendronate

Morphological changes induced by advanced glycation endproducts in osteoblastic cells: Effects of co-incubation with alendronate

Rutin Prevents High Glucose-Induced Renal Glomerular Endothelial Hyperpermeability by Inhibiting the ROS/Rhoa/ROCK Signaling Pathway

Elevated Glucose Levels Promote Contractile and Cytoskeletal Gene Expression in Vascular Smooth Muscle via Rho/Protein Kinase C and Actin Polymerization

Contact Info

Product

Resources

About