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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Dai, Chunsun Stolz, Donna B. Kiss, Lawrence P. Monga, Satdarshan P. Holzman, Lawrence B. Liu, Youhua |
| Description | Country affiliation: United States Author Affiliation: Dai C ( Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.) |
| Abstract | Podocyte dysfunction, one of the major causes of proteinuria, leads to glomerulosclerosis and end stage renal disease, but its underlying mechanism remains poorly understood. Here we show that Wnt/beta-catenin signaling plays a critical role in podocyte injury and proteinuria. Treatment with adriamycin induced Wnt and activated beta-catenin in mouse podocytes. Overexpression of Wnt1 in vivo activated glomerular beta-catenin and aggravated albuminuria and adriamycin-induced suppression of nephrin expression, whereas blockade of Wnt signaling with Dickkopf-1 ameliorated podocyte lesions. Podocyte-specific knockout of beta-catenin protected against development of albuminuria after injury. Moreover, pharmacologic activation of beta-catenin induced albuminuria in wild-type mice but not in beta-catenin-knockout littermates. In human proteinuric kidney diseases such as diabetic nephropathy and focal segmental glomerulosclerosis, we observed upregulation of Wnt1 and active beta-catenin in podocytes. Ectopic expression of either Wnt1 or stabilized beta-catenin in vitro induced the transcription factor Snail and suppressed nephrin expression, leading to podocyte dysfunction. These results suggest that targeting hyperactive Wnt/beta-catenin signaling may represent a novel therapeutic strategy for proteinuric kidney diseases. |
| File Format | HTM / HTML |
| ISSN | 10466673 |
| e-ISSN | 15333450 |
| DOI | 10.1681/ASN.2009010019 |
| Journal | Journal of the American Society of Nephrology |
| Issue Number | 9 |
| Volume Number | 20 |
| Language | English |
| Publisher | American Society of Nephrology |
| Publisher Date | 2009-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Nephrology Albuminuria Metabolism Pathology Podocytes Wnt1 Protein Beta Catenin Animals Biopsy Cell Line, Transformed Diabetic Nephropathies Glomerulosclerosis, Focal Segmental Membrane Proteins Genetics Mice Mice, Inbred Balb C Mice, Inbred C57bl Mice, Knockout Cytology Signal Transduction Physiology Transcription Factors Up-regulation Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Nephrology |
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