title: Glycated serum albumin stimulates expression of endothelial cell specific molecule-1 in human umbilical vein endothelial cells: Implication in diabetes mediated endothelial dysfunction.
abstract: Pro-inflammatory conditions induced by products of protein glycation in diabetes substantially enhance the risk of endothelial dysfunction and related vascular complications. Endothelial cell specific molecule-1 (ESM-1) or endocan has been demonstrated as a potential biomarker in cancer and sepsis. Its role in diabetes-induced pathologies remains unknown. The expression of ESM-1 gene is under cytokine regulation, indicating its role in endothelium-dependent pathological disorders. In this study, we investigated the effect of advanced glycated human serum albumin (AGE-HSA) on the production of ESM-1. We show that AGE-HSA exerts a modulating role on the expression of ESM-1 in human umbilical vein endothelial cells. It up-regulates expression of ESM-1 protein in a dose-dependent manner which correlates with its messenger RNA (mRNA) transcription. RAGE and galectin-3, both AGE receptors, show antagonistic action on its expression. While gene silencing of RAGE has down-regulatory effect, that of galectin-3 has up-regulatory effect on AGE-induced expression of ESM-1. Inhibition of MAPKKK and JNK pathways did not alter the expression. In contrast, phosphatidylinositol 3 kinase (PI3K) inhibition significantly up-regulated ESM-1 expression. In conclusion, these results suggest that AGE-induced activation of human umbilical vein endothelial cells promotes formation of endocan which is an endothelial dysfunction marker and may be related to vascular disease in diabetes.
authors.affiliation: Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, India.
authors.forename: Bikesh K
authors.initials: BK
authors.lastname: Nirala
authors.affiliation: Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi, India.
authors.forename: Vivekanandan
authors.initials: V
authors.lastname: Perumal
authors.affiliation: Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, India nkarm@yahoo.com.
authors.forename: Nivedita K
authors.initials: NK
authors.lastname: Gohil
mesh_terms: D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D037502:Galectin 3 / Q000187:drug effects / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000187:drug effects / Q000378:metabolism; D009363:Neoplasm Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011509:Proteoglycans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000067759:Receptor for Advanced Glycation End Products / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012709:Serum Albumin / Q000494:pharmacology*; D015398:Signal Transduction; D000093423:Glycated Serum Albumin
chemical_list: C000593871:AGER protein, human; C101134:ESM1 protein, human; D037502:Galectin 3; D017127:Glycation End Products, Advanced; D009363:Neoplasm Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011509:Proteoglycans; D000067759:Receptor for Advanced Glycation End Products; D012709:Serum Albumin; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; D000093423:Glycated Serum Albumin
keywords: Endothelial cell specific molecule-1; advanced glycation end product; diabetes; galectin-3; serum albumin