Post-transcriptional up-regulation of Tsc-22 by Ybx1, a target of miR-216a, mediates TGF-{beta}-induced collagen expression in kidney cells.
J Biol Chem
; 285(44): 34004-15, 2010 Oct 29.
Article
em En
| MEDLINE
| ID: mdl-20713358
ABSTRACT
Increased accumulation of extracellular matrix proteins and hypertrophy induced by transforming growth factor-ß1 (TGF-ß) in renal mesangial cells (MC) are hallmark features of diabetic nephropathy. Although the post-transcriptional regulation of key genes has been implicated in these events, details are not fully understood. Here we show that TGF-ß increased microRNA-216a (miR-216a) levels in mouse MC, with parallel down-regulation of Ybx1, a miR-216a target and RNA-binding protein. TGF-ß also enhanced protein levels of Tsc-22 (TGF-ß-stimulated clone 22) and collagen type I α-2 (Col1a2) expression in MC through far upstream enhancer E-boxes by interaction of Tsc-22 with an E-box regulator, Tfe3. Ybx1 colocalized with processing bodies in MC and formed a ribonucleoprotein complex with Tsc-22 mRNA, and this complex formation was reduced by TGF-ß, miR-216a mimics, or Ybx1 shRNA to increase Tsc-22 protein levels but enhanced by miR-216a inhibitor oligonucleotides. Chromatin immunoprecipitation (ChIP) assays revealed that TGF-ß could increase the occupancies of Tsc-22 and Tfe3 on enhancer E-boxes of Col1a2. Co-immunoprecipitation assays revealed that TGF-ß promoted the interaction of Tsc-22 with Tfe3. These results demonstrate that post-transcriptional regulation of Tsc-22 mediated through Ybx1, a miR-216a target, plays a key role in TGF-ß-induced Col1a2 in MC related to the pathogenesis of diabetic nephropathy.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Fatores de Transcrição
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Regulação da Expressão Gênica
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Fator de Crescimento Transformador beta
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MicroRNAs
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Rim
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos