Linked Life Data

20709030

Source:http://linkedlifedata.com/resource/pubmed/id/20709030

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2010-9-27
pubmed:abstractText
MicroRNAs (miRNAs) are abundantly expressed in the brain and play an important role in disorders of the brain, including Alzheimer's diseases (AD). Growing body of evidence suggests that the TGF-? signaling pathway plays a key role in the pathogenesis of AD. However, it is unclear whether miRNAs involved in AD pathogenesis by regulating TGF-? signaling. Here we found that miR-106b and TGF-? type II receptor (T?R II) were aberrantly expressed in APPswe/PS?E9 mice (a double transgenic mouse model for AD). Sequence analysis revealed two putative binding sites for miR-106b in the 3' UTR of the T?R II mRNA. Our results showed that the expression of miR-106b was inversely correlated with T?R II protein levels and miR-106b can directly inhibit the T?R II translation in vitro. After induced neurodifferentiation with all-trans retinoic acid, we observed significant neurodegeneration in SH-SY5Y cells stably transfected with miR-106b. Western blot analysis revealed unchanged total Smad2/3 protein levels, but reduced phospho-Smad2/3 (p-Smad2/3) and increased Smad6/7 protein levels in the miR-106b stably transfected cell line. Exposure of SH-SY5Y cells to A?42 oligomers led to the expression of miR-106b was first increased and then decreased and T?R II levels reduced. Our in vitro results suggested that A?42 oligomer-induced miR-106b leads to impairment in TGF-? signaling through T?R II, concomitant with retinoic acid-induced neurodegeneration in SH-SY5Y cells. These results show that T?R II is a functional target of miR-106b and that miR-106b may influence TGF-? signaling, thereby contributing to the pathogenesis of AD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1872-6240
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
21
pubmed:volume
1357
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
166-74
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
miR-106b aberrantly expressed in a double transgenic mouse model for Alzheimer's disease targets TGF-? type II receptor.
pubmed:affiliation
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory of Human Disease Animal Model, State Administration of Tranditional Chinese Medicine, No 5, Panjiayuan, Nanli, Chaoyang District, Beijing 10021, PR China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't