Advanced Glycated End-Products Affect HIF-Transcriptional Activity in Renal Cells

• DOI: 10.1210/me.2013-1036
• Publication Date: 2013-09-13T03:58:44Z
• Authors: Tzvetanka Bondeva; Juliane Heinzig; Carola Ruhe; Gunter Wolf
• Keywords: Transcriptional activity

Advanced glycated end-products (AGEs) are ligands of the receptor for AGEs and increase in diabetic disease. MAPK organizer 1 (Morg1) via its binding partner prolyl-hydroxylase domain (PHD)-3 presumably plays a role regulation hypoxia-inducible factor (HIF)-1α HIF-2α transcriptional activation. The purpose this study was to analyze influence on Morg1 expression correlation PHD3 activity HIF-transcriptional various renal cell types. addition BSA (AGE-BSA) significantly up-regulated mRNA levels murine mesangial cells down-regulated it proximal tubular differentiated podocytes. These effects were reversible when preincubated with α-AGE antibody. AGE-BSA treatment induced relocalization cellular distribution compared nonglycated control-BSA. Analysis demonstrated an elevated enzymatic but inhibition podocytes after AGE-BSA. also affected by treatment. Reporter gene assays EMSAs showed that regulate HIF- under nonhypoxic conditions type-specific manner. In cells, stimulation mainly HIF-1α lesser extent HIF-2α. We detected increased proteins kidneys from heterozygous (HZ) placebo mice wild-type (WT) placebo-treated mice, protein HZ streptozotocin-treated higher than WT mice. isolated (±) inhibited only one allele. findings important better understanding molecular mechanisms nephropathy.