PMID- 22297492
OWN - NLM
STAT- MEDLINE
DCOM- 20120509
LR  - 20211203
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 53
IP  - 3
DP  - 2012 Mar 26
TI  - Suppression of type I collagen expression by miR-29b via PI3K, Akt, and Sp1 
      pathway in human Tenon's fibroblasts.
PG  - 1670-8
LID - 10.1167/iovs.11-8670 [doi]
AB  - PURPOSE: To evaluate the expression profile of microRNAs (miRNAs) and their roles 
      in human Tenon's fibroblasts (HTFs), and to establish an miRNA-based 
      gene-silencing method for antifibrosis in vitro. METHODS: The miRNA expression 
      profile was analyzed by microarray using quiescent and transforming growth factor 
      beta 1 (TGFbeta1)-stimulated primary HTFs, respectively. Candidate miRNAs were 
      identified by quantitative RT-PCR. miRNAs potentially targeting fibrosis-related 
      genes were predicted using a published algorithm. Predicted fibrosis-related 
      genes regulated by candidate miRNAs were confirmed by transfection of the miRNA 
      into HTF culture (with or without TGFbeta1 treatment), followed by quantitative 
      RT-PCR and Western blot analysis. RESULTS: In all, 38 miRNAs were identified to 
      be upregulated and 31 downregulated, in TGFbeta1-stimulated HTFs. Among those, the 
      miR-29b, downregulated in TGFbeta1-treated HTFs, targeted a cadre of mRNAs that 
      encode proteins involved in fibrosis, including PI3Kp85alpha, Sp1, and collagen type 
      I alpha1 (Col1A1). Treatment of HTFs with TGFbeta1 activated the PI3K/Akt/Sp1 
      pathway and, consequently, induced an increase in the expression of type I 
      collagen. Overexpression of miR-29b inhibited the PI3K/Akt/Sp1 pathway, and 
      attenuated the expression of Col1A1. CONCLUSIONS. miR-29b acted as a suppressor 
      of type I collagen gene by repressing the PI3K/Akt/Sp1 pathway in HTFs. 
      Overexpression of miR-29b protected subconjunctival tissues against collagen 
      production and fibrosis. These findings provided a novel rationale for the 
      development of miRNA-based strategies for attenuating scar formation after 
      glaucoma filtering surgery.
FAU - Li, Ning
AU  - Li N
AD  - Department of Ophthalmology, Second Xiangya Hospital, Central South University, 
      Changsha, Hunan Province, People's Republic of China.
FAU - Cui, Juanlian
AU  - Cui J
FAU - Duan, Xuanchu
AU  - Duan X
FAU - Chen, Huihui
AU  - Chen H
FAU - Fan, Fang
AU  - Fan F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120326
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Collagen Type I)
RN  - 0 (Collagen Type I, alpha 1 Chain)
RN  - 0 (MIRN29a microRNA, human)
RN  - 0 (MicroRNAs)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (Sp1 kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Blotting, Western
MH  - Collagen Type I/*metabolism
MH  - Collagen Type I, alpha 1 Chain
MH  - Down-Regulation
MH  - Fibroblasts/*metabolism
MH  - Gene Silencing
MH  - Humans
MH  - MicroRNAs/*physiology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Protein Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tenon Capsule/*metabolism
MH  - Up-Regulation
EDAT- 2012/02/03 06:00
MHDA- 2012/05/10 06:00
CRDT- 2012/02/03 06:00
PHST- 2012/02/03 06:00 [entrez]
PHST- 2012/02/03 06:00 [pubmed]
PHST- 2012/05/10 06:00 [medline]
AID - iovs.11-8670 [pii]
AID - 10.1167/iovs.11-8670 [doi]
PST - epublish
SO  - Invest Ophthalmol Vis Sci. 2012 Mar 26;53(3):1670-8. doi: 10.1167/iovs.11-8670.