Blockade of Wnt/β-catenin signaling by paricalcitol ameliorates proteinuria and kidney injury
- Authors
- He W.; Kang Y.S.; Dai C.; Liu Y.
- Issue Date
- 2011
- Citation
- Journal of the American Society of Nephrology, v.22, no.1, pp 90 - 103
- Pages
- 14
- Indexed
- SCI
SCIE
SCOPUS
- Journal Title
- Journal of the American Society of Nephrology
- Volume
- 22
- Number
- 1
- Start Page
- 90
- End Page
- 103
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/14152
- DOI
- 10.1681/ASN.2009121236
- ISSN
- 1046-6673
1533-3450
- Abstract
- Recent studies implicate Wnt/β-catenin signaling in podocyte dysfunction. Because vitamin D analogs can inhibit β-catenin in other tissues, we tested whether the vitamin D analog paricalcitol could ameliorate podocyte injury, proteinuria, and renal fibrosis in adriamycin (ADR) nephropathy. Compared with vehicle-treated controls, paricalcitol preserved expression of nephrin, podocin, and WT1; prevented proteinuria; and reduced glomerulosclerotic lesions induced by ADR. Paricalcitol also inhibited expression of proinflammatory cytokines, reduced renal infiltration of monocytes/macrophages, hampered activation of renal myofibroblasts, and suppressed expression of the fibrogenic TGF-β1, CTGF, fibronectin, and types I and III collagen. Selective suppression of renal Wnt4, Wnt7a, Wnt7b, and Wnt10a expression after ADR accompanied these renoprotective effects of paricalcitol. Significant upregulation of β-catenin, predominantly in podocytes and tubular epithelial cells, accompanied renal injury; paricalcitol largely abolished this induction of renal β-catenin and inhibited renal expression of Snail, a downstream effector of Wnt/β-catenin signaling. Administration of paricalcitol also ameliorated established proteinuria. In vitro, paricalcitol induced a physical interaction between the vitamin D receptor and β-catenin in podocytes, which led to suppression of β-catenin-mediated gene transcription. In summary, these findings suggest that paricalcitol prevents podocyte dysfunction, proteinuria, and kidney injury in adriamycin nephropathy by inhibiting Wnt/β-catenin signaling. Copyright © 2011 by the American Society of Nephrology.
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Collections - 2. Clinical Science > Department of Nephrology and Hypertension > 1. Journal Articles
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