Abstract：
:Microalbuminuria is a primary manifestation of diabetic nephropathy. Endothelial cell-selective adhesion molecule (ESAM) is a new member of the immunoglobulin superfamily which is selectively expressed by vascular endothelial cells. Although ESAM mediates homophilic interaction between endothelial cells, the role of ESAM in glomerular permeability remains unknown. We examined the expression and function of ESAM in the high glucose-induced microangiopathy in the kidney. ESAM was highly expressed in the glomerular endothelial cells, and the level was significantly reduced in the streptozotocin-induced diabetic mice. Stimulation of cultured endothelial cells with high glucose (35 mmol/l) resulted in a significant decrease in the ESAM expression compared to normal glucose (5.5 mmol/l). In vitro permeability assays revealed that albumin diffusion across endothelial monolayers was significantly increased when ESAM was knocked down by siRNA, suggesting that ESAM regulates vascular permeability of the glomeruli. To confirm these results in vivo, albuminuria was assessed using ESAM-/- mice. Urinary albumin to creatinine ratio in ESAM-/- mice was significantly higher than in ESAM+/+ mice. Transmission electron microscopy revealed that glomerular endothelial fenestration was decreased and endothelial tight junction was irregular and relatively wider in ESAM-/- mice than in ESAM+/+ mice. In conclusion, hyperglycemia downregulates ESAM and increases glomerular endothelial permeability. Thus, ESAM may regulate albumin extravasation at the glomeruli and play a role in the initiation of diabetic nephropathy.
journal_name
Microvasc Resjournal_title
Microvascular researchauthors
Hara T,Ishida T,Cangara HM,Hirata Kdoi
10.1016/j.mvr.2009.01.002subject
Has Abstractpub_date
2009-05-01 00:00:00pages
348-55issue
3eissn
0026-2862issn
1095-9319pii
S0026-2862(09)00007-7journal_volume
77pub_type
杂志文章abstract：:Injection of labeled microspheres is an established method in animal models to analyze the capillary organ blood flow at different time points. However, the microspheres can lead to stenoses of the capillary lumen, which might affect tissue oxygen supply. Our study aimed to investigate the influence of repeated inject...
journal_title：Microvascular research
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journal_title：Microvascular research
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journal_title：Microvascular research
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journal_title：Microvascular research
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journal_title：Microvascular research
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journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1006/mvre.1994.1028
更新日期：1994-05-01 00:00:00
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doi：10.1016/j.mvr.2012.06.003
更新日期：2012-09-01 00:00:00
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journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1016/j.mvr.2004.08.003
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journal_title：Microvascular research
pub_type： 杂志文章
doi：10.1006/mvre.1993.1042
更新日期：1993-09-01 00:00:00
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doi：10.1016/j.mvr.2015.05.004
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doi：10.1006/mvre.1999.2208
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journal_title：Microvascular research
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journal_title：Microvascular research
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doi：10.1006/mvre.1998.2105
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journal_title：Microvascular research
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abstract：:Endotoxemia, a major feature of sepsis, is a common cause of acute lung injury and initiates rapid accumulation of leukocytes in the lung vasculature. Endothelial mechanisms that underlie this accumulation remain unclear, as current experimental models of endotoxemia are less suitable for targeted activation of the en...
journal_title：Microvascular research
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doi：10.1016/j.mvr.2012.01.006
更新日期：2012-05-01 00:00:00
