title: High glucose induces podocyte injury via enhanced (pro)renin receptor-Wnt-β-catenin-snail signaling pathway.
abstract: (Pro)renin receptor (PRR) expression is upregulated in diabetes. We hypothesized that PRR contributes to podocyte injury via activation of Wnt-β-catenin-snail signaling pathway. Mouse podocytes were cultured in normal (5 mM) or high (25 mM) D-glucose for 3 days. Compared to normal glucose, high glucose significantly decreased mRNA and protein expressions of podocin and nephrin, and increased mRNA and protein expressions of PRR, Wnt3a, β-catenin, and snail, respectively. Confocal microscopy studies showed significant reduction in expression and reorganization of podocyte cytoskeleton protein, F-actin, in response to high glucose. Transwell functional permeability studies demonstrated significant increase in albumin flux through podocytes monolayer with high glucose. Cells treated with high glucose and PRR siRNA demonstrated significantly attenuated mRNA and protein expressions of PRR, Wnt3a, β-catenin, and snail; enhanced expressions of podocin mRNA and protein, improved expression and reorganization of F-actin, and reduced transwell albumin flux. We conclude that high glucose induces podocyte injury via PRR-Wnt-β-catenin-snail signaling pathway.
authors.affiliation: Division of Endocrinology and Metabolism, University of Virginia Health System, Charlottesville, Virginia, United States of America.
authors.forename: Caixia
authors.initials: C
authors.lastname: Li
authors.affiliation: Division of Endocrinology and Metabolism, University of Virginia Health System, Charlottesville, Virginia, United States of America.
authors.forename: Helmy M
authors.initials: HM
authors.lastname: Siragy
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D005947:Glucose / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D051379:Mice; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D000071250:Snail Family Transcription Factors; D013549:Sweetening Agents / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*; D000093342:Prorenin Receptor
chemical_list: D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D000071250:Snail Family Transcription Factors; D013549:Sweetening Agents; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; D005947:Glucose; D000093342:Prorenin Receptor