Dataset Information

Growth factor TGF-? induces intestinal epithelial cell (IEC-6) differentiation: miR-146b as a regulatory component in the negative feedback loop.

ABSTRACT: TGF-? is a potent pleiotropic factor that promotes small intestinal cell differentiation. The role of microRNAs in the TGF-? induction of intestinal epithelial phenotype is largely unknown. We hypothesized that microRNAs are functionally involved in TGF-?-induced intestinal cell growth. In this study, TGF-? caused a morphological change of IEC-6 cells and stimulated expression of the epithelial cell markers alkaline phosphatase, villin, and aminopeptidase N. By global microRNA profiling during TGF-?-induced intestinal crypt cell (IEC-6) differentiation, we identified 19 differentially expressed microRNAs. We showed by real-time Q-PCR that miR-146b expression increased rapidly after TGF-? treatment; sequence analysis and in vitro assays revealed that miR-146b targets SIAH2, an E3 ubiquitin ligase, with decreased protein expression upon IEC-6 cell differentiation. Transfection of miR-146b inhibitor before TGF-? treatment blocked the down-regulation of SIAH2 in response to TGF-?. Moreover, SIAH2 over-expression during TGF-? treatment caused a significant decrease in Smad7 protein expression in IEC-6 cells. Furthermore, activation of the ERK1/2 pathway is active in the up-regulation of miR-146b by TGF-?. These findings suggest a novel mechanism whereby TGF-? signaling during IEC-6 cell differentiation may be modulated in part by microRNAs, and we propose a key role for miR-146b in the homeostasis of growth factor TGF-? signaling through a negative feedback regulation involving down-regulation of SIAH2 repressed Smad7 activities.

SUBMITTER: Liao Y

PROVIDER: S-EPMC3534992 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Growth factor TGF-β induces intestinal epithelial cell (IEC-6) differentiation: miR-146b as a regulatory component in the negative feedback loop.

Liao Yalin Y Zhang Man M Lönnerdal Bo B

Genes & nutrition 20120509 1

TGF-β is a potent pleiotropic factor that promotes small intestinal cell differentiation. The role of microRNAs in the TGF-β induction of intestinal epithelial phenotype is largely unknown. We hypothesized that microRNAs are functionally involved in TGF-β-induced intestinal cell growth. In this study, TGF-β caused a morphological change of IEC-6 cells and stimulated expression of the epithelial cell markers alkaline phosphatase, villin, and aminopeptidase N. By global microRNA profiling during T ...[more]

PMID: 22570175

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Dataset Information

Growth factor TGF-? induces intestinal epithelial cell (IEC-6) differentiation: miR-146b as a regulatory component in the negative feedback loop.

Publications

Growth factor TGF-β induces intestinal epithelial cell (IEC-6) differentiation: miR-146b as a regulatory component in the negative feedback loop.

Similar Datasets

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