Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
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Target Concepts:
Gene/Protein
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Query: UMLS:C0730345 (
microalbuminuria
)
4,018
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Endothelial cell-selective adhesion molecule regulates albuminuria in diabetic nephropathy. 1932 80