PMID- 22976296
OWN - NLM
STAT- MEDLINE
DCOM- 20130828
LR  - 20211203
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Linking)
VI  - 125
IP  - Pt 23
DP  - 2012 Dec 1
TI  - CCN2/CTGF increases expression of miR-302 microRNAs, which target the TGFbeta type 
      II receptor with implications for nephropathic cell phenotypes.
PG  - 5621-9
LID - 10.1242/jcs.105528 [doi]
AB  - Signalling interplay between transforming growth factor-beta (TGFbeta) and CCN2 [also 
      called connective tissue growth factor (CTGF)] plays a crucial role in the 
      progression of diabetic nephropathy and has been implicated in cellular 
      differentiation. To investigate the potential role of microRNAs (miRNAs) in the 
      mediation of this signalling network, we performed miRNA screening in mesangial 
      cells treated with recombinant human CCN2. Analysis revealed a cohort of 22 
      miRNAs differentially expressed by twofold or more, including members of the 
      miR-302 family. Target analysis of miRNA to 3'-untranslated regions (3'-UTRs) 
      identified TGFbeta receptor II (TbetaRII) as a potential miR-302 target. In mesangial 
      cells, decreased TbetaRII expression was confirmed in response to CCN2 together with 
      increased expression of miR-302d. TbetaRII was confirmed as an miR-302 target, and 
      inhibition of miR-302d was sufficient to attenuate the effect of CCN2 on TbetaRII. 
      Data from the European Renal cDNA Biopsy Bank revealed decreased TbetaRII in 
      diabetic patients, suggesting pathophysiological significance. In a mouse model 
      of fibrosis (UUO), miR-302d was increased, with decreased TbetaRII expression and 
      aberrant signalling, suggesting relevance in chronic fibrosis. miR-302d decreased 
      TGFbeta-induced epithelial mesenchymal transition (EMT) in renal HKC8 epithelial 
      cells and attenuated TGFbeta-induced mesangial production of fibronectin and 
      thrombospondin. In summary, we demonstrate a new mode of regulation of TGFbeta by 
      CCN2, and conclude that the miR-302 family has a role in regulating growth factor 
      signalling pathways, with implications for nephropathic cell fate transitions.
FAU - Faherty, Noel
AU  - Faherty N
AD  - UCD Diabetes Research Centre, UCD Conway Institute, University College Dublin, 
      Belfield, Dublin 4, Ireland.
FAU - Curran, Simon P
AU  - Curran SP
FAU - O'Donovan, Helen
AU  - O'Donovan H
FAU - Martin, Finian
AU  - Martin F
FAU - Godson, Catherine
AU  - Godson C
FAU - Brazil, Derek P
AU  - Brazil DP
FAU - Crean, John K
AU  - Crean JK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120912
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (MicroRNAs)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta)
RN  - 139568-91-5 (Connective Tissue Growth Factor)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type II)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Connective Tissue Growth Factor/*pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - Male
MH  - Mesangial Cells/drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/*genetics
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Receptor, Transforming Growth Factor-beta Type II
MH  - Receptors, Transforming Growth Factor beta/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transforming Growth Factor beta/metabolism
EDAT- 2012/09/15 06:00
MHDA- 2013/08/29 06:00
CRDT- 2012/09/15 06:00
PHST- 2012/09/15 06:00 [entrez]
PHST- 2012/09/15 06:00 [pubmed]
PHST- 2013/08/29 06:00 [medline]
AID - jcs.105528 [pii]
AID - 10.1242/jcs.105528 [doi]
PST - ppublish
SO  - J Cell Sci. 2012 Dec 1;125(Pt 23):5621-9. doi: 10.1242/jcs.105528. Epub 2012 Sep 
      12.