PMID- 32694556
OWN - NLM
STAT- MEDLINE
DCOM- 20210324
LR  - 20210721
IS  - 2041-4889 (Electronic)
VI  - 11
IP  - 7
DP  - 2020 Jul 21
TI  - CircRNA TADA2A relieves idiopathic pulmonary fibrosis by inhibiting proliferation 
      and activation of fibroblasts.
PG  - 553
LID - 10.1038/s41419-020-02747-9 [doi]
LID - 553
AB  - The excessive activation and proliferation of lung fibroblasts are responsible 
      for the abundant deposition of extracellular matrix (ECM) in idiopathic pulmonary 
      fibrosis (IPF), while its specific mechanism is still unknown. This study focuses 
      on the role of circRNA (circ) TADA2A in functional abnormalities of lung 
      fibroblasts and aims to elaborate its regulatory mechanism. In the present study, 
      circTADA2A was downregulated in both IPF primary human lung fibroblasts and human 
      IPF fibroblastic cell lines. Functionally, the overexpression of circTADA2A 
      repressed the activation and proliferation of normal human fibroblastic cell line 
      induced by several fibrogenic growth factors. Using fluorescence in situ 
      hybridization (FISH), luciferase reporter assays, and RNA pull-down, circTADA2A 
      was confirmed to function as sponges of miR-526b and miR-203, thus releasing the 
      expression of Caveolin (Cav)-1 and Cav2. The overexpression of circTADA2A 
      suppressed lung-fibroblasts activation via Cav1 and reduced lung-fibroblasts 
      proliferation via Cav2. In vivo experiments also confirmed that the 
      overexpression of circTADA2A decreased fibrogenic responses induced by bleomycin 
      in lung-fibrosis mice. Collectively, circTADA2A repressed lung-fibroblasts 
      activation via miR-526b/Cav1 and reduced lung-fibroblasts proliferation via 
      miR-203/Cav2, thus inhibiting the excessive deposition of ECM and relieving IPF.
FAU - Li, Juan
AU  - Li J
AD  - Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou 
      University, 450052, Zhengzhou, China.
FAU - Li, Ping
AU  - Li P
AD  - Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou 
      University, 450052, Zhengzhou, China.
FAU - Zhang, Guojun
AU  - Zhang G
AD  - Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou 
      University, 450052, Zhengzhou, China.
FAU - Qin, Pan
AU  - Qin P
AD  - Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou 
      University, 450052, Zhengzhou, China.
FAU - Zhang, Da
AU  - Zhang D
AD  - Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou 
      University, 450052, Zhengzhou, China.
FAU - Zhao, Wei
AU  - Zhao W
AD  - Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou 
      University, 450052, Zhengzhou, China. fcczhaow@zzu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200721
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Caveolins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Circular)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Base Sequence
MH  - Caveolins/metabolism
MH  - Cell Line
MH  - Cell Proliferation/drug effects/genetics
MH  - Down-Regulation/genetics
MH  - Fibroblasts/drug effects/*metabolism/*pathology
MH  - Humans
MH  - Idiopathic Pulmonary Fibrosis/*genetics/*pathology
MH  - Intercellular Signaling Peptides and Proteins/pharmacology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/genetics/metabolism
MH  - Middle Aged
MH  - RNA, Circular/genetics/*metabolism
PMC - PMC7374112
COIS- The authors declare that they have no conflict of interest.
EDAT- 2020/07/23 06:00
MHDA- 2021/03/25 06:00
PMCR- 2020/07/21
CRDT- 2020/07/23 06:00
PHST- 2019/12/02 00:00 [received]
PHST- 2020/07/03 00:00 [accepted]
PHST- 2020/07/01 00:00 [revised]
PHST- 2020/07/23 06:00 [entrez]
PHST- 2020/07/23 06:00 [pubmed]
PHST- 2021/03/25 06:00 [medline]
PHST- 2020/07/21 00:00 [pmc-release]
AID - 10.1038/s41419-020-02747-9 [pii]
AID - 2747 [pii]
AID - 10.1038/s41419-020-02747-9 [doi]
PST - epublish
SO  - Cell Death Dis. 2020 Jul 21;11(7):553. doi: 10.1038/s41419-020-02747-9.