PMID- 32585629
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210110
IS  - 2162-2531 (Print)
IS  - 2162-2531 (Electronic)
IS  - 2162-2531 (Linking)
VI  - 21
DP  - 2020 Sep 4
TI  - miR-301a Suppression within Fibroblasts Limits the Progression of Fibrosis 
      through the TSC1/mTOR Pathway.
PG  - 217-228
LID - S2162-2531(20)30153-0 [pii]
LID - 10.1016/j.omtn.2020.05.027 [doi]
AB  - Pulmonary fibrosis has been characterized by abnormal proliferation of 
      fibroblasts and massive deposition of the extracellular matrix, which results 
      from a complex interplay of chronic injury and inflammatory responses. 
      MicroRNA-301a (miR-301a) is activated by multiple inflammatory stimulators, 
      contributing to multiple tumorigenesis and autoimmune diseases. This study showed 
      that miR-301a was overexpressed in a bleomycin-induced murine model of pulmonary 
      fibrosis and patients with idiopathic pulmonary fibrosis (IPF). In addition, 
      miR-301a was activated by transforming growth factor beta (TGF-beta) and interleukin 6 
      (IL-6) in normal and IPF fibroblasts, which was markedly reversed by the signal 
      transducer and activator of transcription 3 (STAT3) inhibitor. The genetic 
      ablation of miR-301a in mice reduced bleomycin-induced lung fibrosis, and the 
      downregulation of miR-301a restrained proliferation and activation of 
      fibroblasts. Furthermore, this study demonstrated that TSC1 was a functional 
      target of miR-301a in fibroblasts, and the negative regulation of TSC1 by 
      miR-301a promoted the severity of pulmonary fibrosis through the mammalian target 
      of rapamycin (mTOR) signaling pathway. The blocking of miR-301a by the 
      intravenous injection of antagomiR-301a inhibited the proliferation of 
      fibroblasts and the structural destruction of lung tissues in the 
      bleomycin-induced lung fibrosis mouse model. The findings revealed the crucial 
      role of the miR-301a/TSC1/mTOR axis in the pathogenesis of pulmonary fibrosis, 
      suggesting that miR-301a might serve as a potential therapeutic target.
CI  - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Wang, Jiexuan
AU  - Wang J
AD  - National Clinical Research Center for Respiratory Disease, State Key Laboratory 
      of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
FAU - Li, Xun
AU  - Li X
AD  - Institute for Brain Research and Rehabilitation, Guangdong Key Laboratory of 
      Mental Health and Cognitive Science, Center for Studies of Psychological 
      Application, South China Normal University, Guangzhou 510631, China.
FAU - Zhong, Mingtian
AU  - Zhong M
AD  - Institute for Brain Research and Rehabilitation, Guangdong Key Laboratory of 
      Mental Health and Cognitive Science, Center for Studies of Psychological 
      Application, South China Normal University, Guangzhou 510631, China.
FAU - Wang, Yansheng
AU  - Wang Y
AD  - National Clinical Research Center for Respiratory Disease, State Key Laboratory 
      of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
FAU - Zou, Liming
AU  - Zou L
AD  - Institute for Brain Research and Rehabilitation, Guangdong Key Laboratory of 
      Mental Health and Cognitive Science, Center for Studies of Psychological 
      Application, South China Normal University, Guangzhou 510631, China.
FAU - Wang, Miaomiao
AU  - Wang M
AD  - Institute for Brain Research and Rehabilitation, Guangdong Key Laboratory of 
      Mental Health and Cognitive Science, Center for Studies of Psychological 
      Application, South China Normal University, Guangzhou 510631, China.
FAU - Gong, Xiaoli
AU  - Gong X
AD  - Institute for Brain Research and Rehabilitation, Guangdong Key Laboratory of 
      Mental Health and Cognitive Science, Center for Studies of Psychological 
      Application, South China Normal University, Guangzhou 510631, China.
FAU - Wang, Xinjie
AU  - Wang X
AD  - Institute for Brain Research and Rehabilitation, Guangdong Key Laboratory of 
      Mental Health and Cognitive Science, Center for Studies of Psychological 
      Application, South China Normal University, Guangzhou 510631, China.
FAU - Zhou, Chengzhi
AU  - Zhou C
AD  - National Clinical Research Center for Respiratory Disease, State Key Laboratory 
      of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China. 
      Electronic address: doctorzcz@163.com.
FAU - Ma, Xiaodong
AU  - Ma X
AD  - Institute for Brain Research and Rehabilitation, Guangdong Key Laboratory of 
      Mental Health and Cognitive Science, Center for Studies of Psychological 
      Application, South China Normal University, Guangzhou 510631, China. Electronic 
      address: sciencema@hotmail.com.
FAU - Liu, Ming
AU  - Liu M
AD  - National Clinical Research Center for Respiratory Disease, State Key Laboratory 
      of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China. 
      Electronic address: mingliu128@hotmail.com.
LA  - eng
PT  - Journal Article
DEP - 20200526
PL  - United States
TA  - Mol Ther Nucleic Acids
JT  - Molecular therapy. Nucleic acids
JID - 101581621
PMC - PMC7321782
OTO - NOTNLM
OT  - TSC1
OT  - mTOR
OT  - miR-301a
OT  - pulmonary fibrosis
EDAT- 2020/06/26 06:00
MHDA- 2020/06/26 06:01
PMCR- 2020/05/26
CRDT- 2020/06/26 06:00
PHST- 2020/04/14 00:00 [received]
PHST- 2020/05/18 00:00 [revised]
PHST- 2020/05/22 00:00 [accepted]
PHST- 2020/06/26 06:00 [pubmed]
PHST- 2020/06/26 06:01 [medline]
PHST- 2020/06/26 06:00 [entrez]
PHST- 2020/05/26 00:00 [pmc-release]
AID - S2162-2531(20)30153-0 [pii]
AID - 10.1016/j.omtn.2020.05.027 [doi]
PST - ppublish
SO  - Mol Ther Nucleic Acids. 2020 Sep 4;21:217-228. doi: 10.1016/j.omtn.2020.05.027. 
      Epub 2020 May 26.