PMID- 25923922
OWN - NLM
STAT- MEDLINE
DCOM- 20160415
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 4
DP  - 2015
TI  - Sp1 Mediates a Therapeutic Role of MiR-7a/b in Angiotensin II-Induced Cardiac 
      Fibrosis via Mechanism Involving the TGF-beta and MAPKs Pathways in Cardiac 
      Fibroblasts.
PG  - e0125513
LID - 10.1371/journal.pone.0125513 [doi]
LID - e0125513
AB  - MicroRNA-7a/b (miR-7a/b) protects cardiac myocytes from apoptosis during 
      ischemia/reperfusion injury; however, its role in angiotensin II (ANG 
      II)-stimulated cardiac fibroblasts (CFs) remains unknown. Therefore, the present 
      study investigated the anti-fibrotic mechanism of miR-7a/b in ANG II-treated CFs. 
      ANG II stimulated the expression of specific protein 1 (Sp1) and collagen I in a 
      dose- and time-dependent manner, and the overexpression of miR-7a/b significantly 
      down-regulated the expression of Sp1 and collagen I stimulated by ANG II (100 nM) 
      for 24 h. miR-7a/b overexpression effectively inhibited MMP-2 expression/activity 
      and MMP-9 expression, as well as CF proliferation and migration. In addition, 
      miR-7a/b also repressed the activation of TGF-beta, ERK, JNK and p38 by ANG II. The 
      inhibition of Sp1 binding activity by mithramycin prevented collagen I 
      overproduction; however, miR-7a/b down-regulation reversed this effect. Further 
      studies revealed that Sp1 also mediated miR-7a/b-regulated MMP expression and CF 
      migration, as well as TGF-beta and ERK activation. In conclusion, miR-7a/b has an 
      anti-fibrotic role in ANG II-treated CFs that is mediated by Sp1 mechanism 
      involving the TGF-beta and MAPKs pathways.
FAU - Li, Rui
AU  - Li R
AD  - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese 
      Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of 
      Shandong University, Jinan, Shandong, China.
FAU - Xiao, Jie
AU  - Xiao J
AD  - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese 
      Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of 
      Shandong University, Jinan, Shandong, China.
FAU - Qing, Xiaoteng
AU  - Qing X
AD  - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese 
      Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of 
      Shandong University, Jinan, Shandong, China.
FAU - Xing, Junhui
AU  - Xing J
AD  - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese 
      Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of 
      Shandong University, Jinan, Shandong, China; Department of Emergency, Qilu 
      Hospital, Shandong University, Jinan, Shandong, China.
FAU - Xia, Yanfei
AU  - Xia Y
AD  - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese 
      Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of 
      Shandong University, Jinan, Shandong, China.
FAU - Qi, Jia
AU  - Qi J
AD  - Department of Cardiology, Central Hospital of Zibo, Shandong, China.
FAU - Liu, Xiaojun
AU  - Liu X
AD  - Department of Cardiology, Central Hospital of Zibo, Shandong, China.
FAU - Zhang, Sen
AU  - Zhang S
AD  - Department of Cardiology, Qilu Hospital of Shandong University, Qingdao, 
      Shandong, China.
FAU - Sheng, Xi
AU  - Sheng X
AD  - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese 
      Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of 
      Shandong University, Jinan, Shandong, China.
FAU - Zhang, Xinyu
AU  - Zhang X
AD  - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese 
      Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of 
      Shandong University, Jinan, Shandong, China.
FAU - Ji, Xiaoping
AU  - Ji X
AD  - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese 
      Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of 
      Shandong University, Jinan, Shandong, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150429
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Collagen Type I)
RN  - 0 (MicroRNAs)
RN  - 0 (Sp1 Transcription Factor)
RN  - 0 (Transforming Growth Factor beta)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.24 (Mmp2 protein, rat)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EC 3.4.24.35 (Mmp9 protein, rat)
RN  - NIJ123W41V (Plicamycin)
SB  - IM
MH  - Angiotensin II/*adverse effects/pharmacology
MH  - Animals
MH  - Cell Movement/drug effects
MH  - Collagen Type I/biosynthesis
MH  - Endomyocardial Fibrosis/chemically induced/*metabolism/pathology
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Fibroblasts/*metabolism/pathology
MH  - Gene Expression Regulation/drug effects
MH  - MAP Kinase Signaling System/drug effects
MH  - Matrix Metalloproteinase 2/biosynthesis
MH  - Matrix Metalloproteinase 9/biosynthesis
MH  - MicroRNAs/*biosynthesis
MH  - Myocardium/*metabolism/pathology
MH  - Plicamycin/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Sp1 Transcription Factor/*metabolism
MH  - Transforming Growth Factor beta/*metabolism
PMC - PMC4414609
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/04/30 06:00
MHDA- 2016/04/16 06:00
PMCR- 2015/04/29
CRDT- 2015/04/30 06:00
PHST- 2014/11/24 00:00 [received]
PHST- 2015/03/12 00:00 [accepted]
PHST- 2015/04/30 06:00 [entrez]
PHST- 2015/04/30 06:00 [pubmed]
PHST- 2016/04/16 06:00 [medline]
PHST- 2015/04/29 00:00 [pmc-release]
AID - PONE-D-14-50476 [pii]
AID - 10.1371/journal.pone.0125513 [doi]
PST - epublish
SO  - PLoS One. 2015 Apr 29;10(4):e0125513. doi: 10.1371/journal.pone.0125513. 
      eCollection 2015.