Linked Life Data

17936263

Source:http://linkedlifedata.com/resource/pubmed/id/17936263

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-11-12
pubmed:abstractText
The mammalian pancreas is known to show a remarkable degree of regenerative ability. Several studies until now have demonstrated that the mammalian pancreas can regenerate in normal as well as diabetic conditions. These studies illustrate that pancreatic transcription factors that are seen to be expressed in a temporal fashion during development are re-expressed during regeneration. The only known exception to this is Neurogenin3 (NGN3). Though NGN3 protein, which marks all the pro-endocrine cells during development, is not seen during mouse pancreas regeneration, functional neo-islets are generated by 4 weeks after 70% pancreatectomy. We observed that pancreatic transcription factors upstream of ngn3 showed similar gene expression patterns during development and regeneration. However, gene transcripts of transcription factors immediately downstream of ngn3 (neuroD and nkx2.2) did not show such similarities in expression. Since NGN3 protein was not detected at any time point during regeneration, we reasoned that post-transcriptional silencing of ngn3 by microRNAs may be a possible mechanism. We carried out microRNA analysis of 283 known and validated mouse microRNAs during different stages of pancreatic development and regeneration and identified that 4 microRNAs; miR-15a, miR-15b, miR-16 and miR-195, which can potentially bind to ngn3 transcript, are expressed at least 200-fold higher in the regenerating mouse pancreas as compared to embryonic day (e) 10.5 or e 16.5 developing mouse pancreas. Inhibition of these miRNAs in regenerating pancreatic cells using anti-sense miRNA-specific inhibitors, induces expression of NGN3 and its downstream players: neuroD and nkx2.2. Similarly, overexpression of miRNAs targeting ngn3 during pancreas development shows reduction in the number of hormone-producing cells. It appears that during pancreatic regeneration in mice, increased expression of these microRNAs allows endocrine regeneration via an alternate pathway that does not involve NGN3 protein. Our studies on microRNA profiling of developing and regenerating pancreas provide us with better understanding of mechanisms that regulate post-natal islet neogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1095-564X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
311
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
603-12
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
MicroRNA profiling of developing and regenerating pancreas reveal post-transcriptional regulation of neurogenin3.
pubmed:affiliation
Stem Cells and Diabetes Section, #10, National Center for Cell Science, Ganeshkhind Road, Pune 411007, India.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't