PMID- 30953355
OWN - NLM
STAT- MEDLINE
DCOM- 20200603
LR  - 20200603
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 234
IP  - 11
DP  - 2019 Nov
TI  - A novel mechanism of Smads/miR-675/TGFbetaR1 axis modulating the proliferation and 
      remodeling of mouse cardiac fibroblasts.
PG  - 20275-20285
LID - 10.1002/jcp.28628 [doi]
AB  - Cardiac fibroblasts (CFs) can over-proliferate during the progression of cardiac 
      fibrosis, accompanied by a net accumulation of extracellular matrix proteins. 
      Based on the profibrotic actions of transforming growth factor beta 1 (TGFbeta1), 
      investigating the mechanisms of TGFbeta1 function in CFs may provide new directions 
      to treatment for cardiac fibrosis. microRNAs (miRNAs) could control CFs 
      proliferation or remodeling via binding to 3'-untranslated region of messenger 
      RNA (mRNA) to negatively regulate gene expression. In the present study, we 
      downloaded several microarray analyses results from GEO attempting to identify 
      miRNAs and possible downstream targets that may be involved in TGF-beta1 function in 
      CFs and to detect the cellular and molecular functions of the identified 
      miRNA-mRNA axis. Here, we identified miR-675 as a downregulated miRNA by TGFbeta1 by 
      bioinformatics analyses and experimental verification. Upon TGFbeta1 stimulation, 
      the protein levels of Alpha-SMAAlpha-SMA, collagen I, and POSTN, and the secreted 
      collagen in the cell culture supernatant significantly increased, whereas the 
      miR-675 expression decreased. Smads mediate TGFbeta1-induced suppression on miR-675 
      via binding miR-675 promoter region. miR-675 overexpression could inhibit, 
      whereas miR-675 inhibition could enhance TGFbeta1-induced mouse CFs (MCF) remodeling 
      and proliferation. TGFbeta receptor 1 (TGFbetaR1), a critical receptor in TGFbeta1/Smad 
      signaling, is a direct downstream target of miR-675. TGFbetaR1 overexpression 
      significantly reverses the effect of miR-675 overexpression on MCF remodeling and 
      proliferation. In summary, miR-675 targets TGFbetaR1 to attenuate TGFbeta1-induced MCF 
      remodeling and proliferation. We demonstrate a novel mechanism of the 
      Smads/miR-675/TGFbetaR1 axis modulating TGFbeta1-induced MCF remodeling and 
      proliferation.
CI  - (c) 2019 Wiley Periodicals, Inc.
FAU - Wang, Lei
AU  - Wang L
AD  - Department of Cardiology, Xiangya Hospital, Central South University, Changsha, 
      Hunan, China.
FAU - Jiang, Ping
AU  - Jiang P
AD  - Department of Cardiology, Zhuzhou Central Hospital, the Affiliated Zhuzhou 
      Hospital of Xiangya Medical College of Central South University, Zhuzhou, Hunan, 
      China.
FAU - He, Yi
AU  - He Y
AD  - Department of Cardiology, Zhuzhou Central Hospital, the Affiliated Zhuzhou 
      Hospital of Xiangya Medical College of Central South University, Zhuzhou, Hunan, 
      China.
FAU - Hu, Hongyu
AU  - Hu H
AD  - Department of Cardiology, Zhuzhou Central Hospital, the Affiliated Zhuzhou 
      Hospital of Xiangya Medical College of Central South University, Zhuzhou, Hunan, 
      China.
FAU - Guo, Yuan
AU  - Guo Y
AD  - Department of Cardiology, Zhuzhou Central Hospital, the Affiliated Zhuzhou 
      Hospital of Xiangya Medical College of Central South University, Zhuzhou, Hunan, 
      China.
FAU - Liu, Xiangyang
AU  - Liu X
AD  - Department of Cardiology, Zhuzhou Central Hospital, the Affiliated Zhuzhou 
      Hospital of Xiangya Medical College of Central South University, Zhuzhou, Hunan, 
      China.
FAU - Qiu, Haihua
AU  - Qiu H
AD  - Department of Cardiology, Zhuzhou Central Hospital, the Affiliated Zhuzhou 
      Hospital of Xiangya Medical College of Central South University, Zhuzhou, Hunan, 
      China.
FAU - Ma, Qilin
AU  - Ma Q
AD  - Department of Cardiology, Xiangya Hospital, Central South University, Changsha, 
      Hunan, China.
FAU - Ouyang, Fan
AU  - Ouyang F
AUID- ORCID: 0000-0002-9922-3241
AD  - Department of Cardiology, Zhuzhou Central Hospital, the Affiliated Zhuzhou 
      Hospital of Xiangya Medical College of Central South University, Zhuzhou, Hunan, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20190405
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (MIRN675 microRNA, mouse)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Messenger)
RN  - 0 (Smad Proteins)
RN  - 0 (Tgfb1 protein, mouse)
RN  - 0 (Transforming Growth Factor beta1)
SB  - IM
MH  - Animals
MH  - Cell Proliferation/physiology
MH  - Cells, Cultured
MH  - Fibroblasts/*metabolism
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/*genetics
MH  - Myocardium/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Signal Transduction/physiology
MH  - Smad Proteins/*metabolism
MH  - Transforming Growth Factor beta1/*metabolism
OTO - NOTNLM
OT  - Smads
OT  - TGFbetaR1
OT  - cardiac fibroblasts
OT  - miR-675
OT  - proliferation
OT  - remodeling
EDAT- 2019/04/07 06:00
MHDA- 2020/06/04 06:00
CRDT- 2019/04/07 06:00
PHST- 2018/11/23 00:00 [received]
PHST- 2019/03/15 00:00 [revised]
PHST- 2019/03/19 00:00 [accepted]
PHST- 2019/04/07 06:00 [pubmed]
PHST- 2020/06/04 06:00 [medline]
PHST- 2019/04/07 06:00 [entrez]
AID - 10.1002/jcp.28628 [doi]
PST - ppublish
SO  - J Cell Physiol. 2019 Nov;234(11):20275-20285. doi: 10.1002/jcp.28628. Epub 2019 
      Apr 5.