PMID- 31175931
OWN - NLM
STAT- MEDLINE
DCOM- 20200507
LR  - 20211204
IS  - 1879-260X (Electronic)
IS  - 0925-4439 (Linking)
VI  - 1865
IP  - 9
DP  - 2019 Sep 1
TI  - The Smad3-miR-29b/miR-29c axis mediates the protective effect of macrophage 
      migration inhibitory factor against cardiac fibrosis.
PG  - 2441-2450
LID - S0925-4439(19)30197-8 [pii]
LID - 10.1016/j.bbadis.2019.06.004 [doi]
AB  - Although macrophage migration inhibitory factor (MIF) is known to have 
      antioxidant property, the role of MIF in cardiac fibrosis has not been well 
      understood. We found that MIF was markedly increased in angiotension II 
      (Ang-II)-infused mouse myocardium. Myocardial function was impaired and cardiac 
      fibrosis was aggravated in Mif-knockout (Mif-KO) mice. Functionally, 
      overexpression of MIF and MIF protein could inhibit the expression of 
      fibrosis-associated collagen (Col) 1a1, COL3A1 and alpha-SMA, and Smad3 activation in 
      mouse cardiac fibroblasts (CFs). Consistently, MIF deficiency could exacerbate 
      the expression of COL1A1, COL3A1 and alpha-SMA, and Smad3 activation in 
      Ang-II-treated CFs. Interestingly, microRNA-29b-3p (miR-29b-3p) and 
      microRNA-29c-3p (miR-29c-3p) were down-regulated in the myocardium of 
      Ang-II-infused Mif-KO mice but upregulated in CFs with MIF overexpression or by 
      treatment with MIF protein. MiR-29b-3p and miR-29c-3p could suppress the 
      expression of COL1A1, COL3A1 and alpha-SMA in CFs through targeting the pro-fibrosis 
      genes of transforming growth factor beta-2 (Tgfb2) and matrix metallopeptidase 2 
      (Mmp2). We further demonstrated that Mif inhibited reactive oxygen species (ROS) 
      generation and Smad3 activation, and rescued the decrease of miR-29b-3p and 
      miR-29c-3p in Ang-II-treated CFs. Smad3 inhibitors, SIS3 and Naringenin, and 
      Smad3 siRNA could reverse the decrease of miR-29b-3p and miR-29c-3p in 
      Ang-II-treated CFs. Taken together, our data demonstrated that the 
      Smad3-miR-29b/miR-29c axis mediates the inhibitory effect of macrophage migration 
      inhibitory factor on cardiac fibrosis.
CI  - Copyright (c) 2019 The Author(s). Published by Elsevier B.V. All rights reserved.
FAU - Liang, Jing-Nan
AU  - Liang JN
AD  - Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangdong 
      Cardiovascular Institute, Guangzhou 510080, China; Research Center of Medical 
      Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical 
      Sciences, Guangzhou 510080, China; School of Pharmacology, Southern Medical 
      University, Guangzhou 510515, China.
FAU - Zou, Xiao
AU  - Zou X
AD  - Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangdong 
      Cardiovascular Institute, Guangzhou 510080, China; Research Center of Medical 
      Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical 
      Sciences, Guangzhou 510080, China.
FAU - Fang, Xian-Hong
AU  - Fang XH
AD  - Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangdong 
      Cardiovascular Institute, Guangzhou 510080, China.
FAU - Xu, Jin-Dong
AU  - Xu JD
AD  - Department of Anesthesiology, Guangdong Cardiovascular Institute, Guangzhou 
      510080, China.
FAU - Xiao, Zhen
AU  - Xiao Z
AD  - Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangdong 
      Cardiovascular Institute, Guangzhou 510080, China; Research Center of Medical 
      Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical 
      Sciences, Guangzhou 510080, China.
FAU - Zhu, Jie-Ning
AU  - Zhu JN
AD  - Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangdong 
      Cardiovascular Institute, Guangzhou 510080, China; Research Center of Medical 
      Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical 
      Sciences, Guangzhou 510080, China.
FAU - Li, Hui
AU  - Li H
AD  - School of Pharmacology, Southern Medical University, Guangzhou 510515, China.
FAU - Yang, Jing
AU  - Yang J
AD  - School of Medicine, South China University of Technology, Guangzhou 510632, 
      China.
FAU - Zeng, Ni
AU  - Zeng N
AD  - School of Medicine, South China University of Technology, Guangzhou 510632, 
      China.
FAU - Yuan, Shu-Jing
AU  - Yuan SJ
AD  - School of Medicine, South China University of Technology, Guangzhou 510632, 
      China.
FAU - Pan, Rong
AU  - Pan R
AD  - School of Biology and Biological Engineering, South China University of 
      Technology, Guangzhou 510632, China.
FAU - Fu, Yong-Heng
AU  - Fu YH
AD  - Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangdong 
      Cardiovascular Institute, Guangzhou 510080, China; Research Center of Medical 
      Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical 
      Sciences, Guangzhou 510080, China.
FAU - Zhang, Ming
AU  - Zhang M
AD  - Research Center of Medical Sciences, Guangdong Provincial People's Hospital, 
      Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
FAU - Luo, Jian-Fang
AU  - Luo JF
AD  - Research Center of Medical Sciences, Guangdong Provincial People's Hospital, 
      Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
FAU - Wang, Sheng
AU  - Wang S
AD  - Department of Anesthesiology, Guangdong Cardiovascular Institute, Guangzhou 
      510080, China.
FAU - Shan, Zhi-Xin
AU  - Shan ZX
AD  - Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangdong 
      Cardiovascular Institute, Guangzhou 510080, China; Research Center of Medical 
      Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical 
      Sciences, Guangzhou 510080, China. Electronic address: shanzhixin@gdph.org.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190606
PL  - Netherlands
TA  - Biochim Biophys Acta Mol Basis Dis
JT  - Biochimica et biophysica acta. Molecular basis of disease
JID - 101731730
RN  - 0 (3' Untranslated Regions)
RN  - 0 (Antigens, Differentiation, B-Lymphocyte)
RN  - 0 (Collagen Type I)
RN  - 0 (Collagen Type I, alpha 1 Chain)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (MIRN29 microRNA, mouse)
RN  - 0 (Macrophage Migration-Inhibitory Factors)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Smad3 Protein)
RN  - 0 (Transforming Growth Factor beta2)
RN  - 0 (invariant chain)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.24 (Mmp2 protein, mouse)
SB  - IM
MH  - 3' Untranslated Regions
MH  - Animals
MH  - Antigens, Differentiation, B-Lymphocyte/chemistry/genetics/metabolism
MH  - Cardiomegaly/pathology/veterinary
MH  - Collagen Type I/metabolism
MH  - Collagen Type I, alpha 1 Chain
MH  - Fibroblasts/cytology/metabolism
MH  - Fibrosis
MH  - Histocompatibility Antigens Class II/chemistry/genetics/metabolism
MH  - Macrophage Migration-Inhibitory Factors/antagonists & 
      inhibitors/genetics/*metabolism
MH  - Male
MH  - Matrix Metalloproteinase 2/chemistry/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - MicroRNAs/chemistry/genetics/*metabolism
MH  - Myocardium/cytology/metabolism
MH  - RNA Interference
MH  - RNA, Small Interfering/metabolism
MH  - Smad3 Protein/*metabolism
MH  - Transforming Growth Factor beta2/chemistry/genetics/metabolism
MH  - Up-Regulation
OTO - NOTNLM
OT  - Cardiac fibrosis
OT  - Macrophage migration inhibitory factor
OT  - MicroRNA-29b-3p
OT  - MicroRNA-29c-3p
OT  - Smad3
EDAT- 2019/06/09 06:00
MHDA- 2020/05/08 06:00
CRDT- 2019/06/09 06:00
PHST- 2019/01/22 00:00 [received]
PHST- 2019/05/15 00:00 [revised]
PHST- 2019/06/03 00:00 [accepted]
PHST- 2019/06/09 06:00 [pubmed]
PHST- 2020/05/08 06:00 [medline]
PHST- 2019/06/09 06:00 [entrez]
AID - S0925-4439(19)30197-8 [pii]
AID - 10.1016/j.bbadis.2019.06.004 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Mol Basis Dis. 2019 Sep 1;1865(9):2441-2450. doi: 
      10.1016/j.bbadis.2019.06.004. Epub 2019 Jun 6.