title: MicroRNA regulation of neuron-like differentiation of adipose tissue-derived stem cells.
abstract: We have reported previously that adipose tissue-derived stem cells (ADSC) could be induced by isobutylmethylxanthine (IBMX) to differentiate into neuron-like cells and such differentiation was mediated by insulin-like growth factor I (IGF-I) signaling. In the present study we show that both IBMX and IGF-I upregulated neural markers beta-III-tubulin and paired-like homeobox transcription factor (Pitx3) in ADSC. Because Pitx3 is important for the maturation and function of dopaminergic neurons and has been shown to be regulated by microRNA miR-133b, we also examined the effects of IBMX and IGF-I on miR-133b expression. The results show that both IBMX and IGF-I upregulated miR-133b expression. When miR-133b was overexpressed in ADSC through transfection of a synthetic microRNA mimic, it caused a downregulation of beta-III-tubulin as evidenced by immunofluorescence staining and western blot analysis. Overexpression of miR-133b also downregulated Pitx3 and IGF-1 receptor (IGF-IR), and all such downregulation occurred at the protein but not the RNA level. The apparent posttranscriptional regulation was subsequently found to be exerted through a potential miR-133b target in the 3'-untranslated region of IGF-IR, as evidenced by luciferase assay. Thus, IGF-I signaling and miR-133b co-regulate potential neural differentiation of ADSC through a feedback mechanism, in which IGF-I upregulates miR-133b while miR-133b in turn downregulates IGF-IR.
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA 94143-0738, USA.
authors.forename: Hongxiu
authors.initials: H
authors.lastname: Ning
authors.forename: Yun-Ching
authors.initials: YC
authors.lastname: Huang
authors.forename: Lia
authors.initials: L
authors.lastname: Banie
authors.forename: Steven
authors.initials: S
authors.lastname: Hung
authors.forename: Guiting
authors.initials: G
authors.lastname: Lin
authors.forename: Long-Cheng
authors.initials: LC
authors.lastname: Li
authors.forename: Tom F
authors.initials: TF
authors.lastname: Lue
authors.forename: Ching-Shwun
authors.initials: CS
authors.lastname: Lin
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D014404:Tubulin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D015056:1-Methyl-3-isobutylxanthine
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