PMID- 20945401
OWN - NLM
STAT- MEDLINE
DCOM- 20110414
LR  - 20211020
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 226
IP  - 5
DP  - 2011 May
TI  - MicroRNA-24 regulates the processing of latent TGFbeta1 during cyclic mechanical 
      stress in human trabecular meshwork cells through direct targeting of FURIN.
PG  - 1407-14
LID - 10.1002/jcp.22476 [doi]
AB  - Cyclic mechanical stress (CMS) leads to alterations of cellular functions in the 
      trabecular meshwork (TM), including the up-regulation of transforming growth 
      factor beta 1 (TGFbeta1), that can potentially contribute to the pathogenesis of 
      glaucoma. Although microRNAs (miRNAs) are known to play important roles in many 
      biological functions, little is known about their potential involvement in the 
      cellular responses elicited by mechanical stress. Here we analyzed changes in 
      miRNA expression induced by CMS, and examined the possible role of miR-24 in the 
      response of human TM cells to CMS. CMS induced the expression of miR-24 that led 
      to the down regulation of the subtilisin-like proprotein convertase FURIN, which 
      is known to play a major role in the processing of TGFbeta1. FURIN was confirmed as 
      a novel target of miR-24 by 3' UTR luciferase assay and western blot. 
      Overexpression of miR-24 resulted in a significant decrease in activated TGFbeta1. 
      This effect was mimicked by down regulation of FURIN by siRNA. Conversely, 
      inhibition of miR-24 expression with a specific antagomir led to a small but 
      significant increase in TGFbeta1. Furthermore, the increase in active TGFbeta1 induced 
      by CMS in HTM cells was prevented by miR-24. Altogether, our results suggest that 
      miRNAs might contribute to the regulation of responses to CMS in TM cells. 
      Specifically, miR-24 might play an important role in modulating the induction of 
      TGFbeta1 mediated by CMS through direct targeting of FURIN.
CI  - Copyright (c) 2010 Wiley-Liss, Inc.
FAU - Luna, Coralia
AU  - Luna C
AD  - Department of Ophthalmology, Duke University, Durham, North Carolina 27710, USA.
FAU - Li, Guorong
AU  - Li G
FAU - Qiu, Jianming
AU  - Qiu J
FAU - Epstein, David L
AU  - Epstein DL
FAU - Gonzalez, Pedro
AU  - Gonzalez P
LA  - eng
GR  - R01 EY016228-05/EY/NEI NIH HHS/United States
GR  - P30 EY005722/EY/NEI NIH HHS/United States
GR  - EY05722/EY/NEI NIH HHS/United States
GR  - EY01894/EY/NEI NIH HHS/United States
GR  - R01 EY016228/EY/NEI NIH HHS/United States
GR  - R01 EY001894/EY/NEI NIH HHS/United States
GR  - EY016228/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (3' Untranslated Regions)
RN  - 0 (4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide)
RN  - 0 (Benzamides)
RN  - 0 (Dioxoles)
RN  - 0 (MIRN24 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Oligonucleotides)
RN  - 0 (TGFB1 protein, human)
RN  - 0 (Transforming Growth Factor beta1)
RN  - EC 3.4.21.75 (FURIN protein, human)
RN  - EC 3.4.21.75 (Furin)
SB  - IM
MH  - 3' Untranslated Regions
MH  - Benzamides/pharmacology
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Dioxoles/pharmacology
MH  - Furin/genetics/*metabolism
MH  - Gene Expression Profiling/methods
MH  - Gene Expression Regulation
MH  - Genes, Reporter
MH  - Humans
MH  - *Mechanotransduction, Cellular/drug effects/genetics
MH  - MicroRNAs/*metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - Oligonucleotides/metabolism
MH  - RNA Interference
MH  - Stress, Mechanical
MH  - Trabecular Meshwork/cytology/drug effects/*enzymology
MH  - Transfection
MH  - Transforming Growth Factor beta1/genetics/*metabolism
PMC - PMC3152464
MID - NIHMS311550
EDAT- 2010/10/15 06:00
MHDA- 2011/04/16 06:00
PMCR- 2011/08/08
CRDT- 2010/10/15 06:00
PHST- 2010/10/15 06:00 [entrez]
PHST- 2010/10/15 06:00 [pubmed]
PHST- 2011/04/16 06:00 [medline]
PHST- 2011/08/08 00:00 [pmc-release]
AID - 10.1002/jcp.22476 [doi]
PST - ppublish
SO  - J Cell Physiol. 2011 May;226(5):1407-14. doi: 10.1002/jcp.22476.