TY - JOUR
T1 - MicroRNA-27a/b mediates endothelin-1-induced PPARγ reduction and proliferation of pulmonary artery smooth muscle cells
AU - Xie, Xinming
AU - Li, Shaojun
AU - Zhu, Yanting
AU - Liu, Lu
AU - Pan, Yilin
AU - Wang, Jian
AU - Shi, Wenhua
AU - Song, Yang
AU - Yang, Lan
AU - Gao, Li
AU - Zang, Weijin
AU - Li, Manxiang
N1 - Funding Information:
Acknowledgement This study was supported by the National Natural Science Foundation of China (Grant No. 81070045).
Publisher Copyright:
© 2017, Springer-Verlag Berlin Heidelberg.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - The down-regulation of peroxisome proliferator-activated receptor γ (PPARγ) expression has been found to correlate with the proliferation of pulmonary artery smooth muscle cells (PASMC), pulmonary vascular remodeling and pulmonary hypertension, while the molecular mechanisms underlying PPARγ reduction in PASMC remain largely unclear. The aim of the current study is to address this issue. Endothelin-1 (ET-1) dose- and time-dependently resulted in PPARγ reduction and proliferation of primary cultured rat PASMC, which was accompanied by the activation of nuclear factor-kappaB (NF-κB) and subsequent induction of microRNA-27a/b (miR-27a/b) expression. Chromatin immunoprecipitation assay revealed that NF-κB directly bound to the promoter regions of miR-27a/b. Luciferase reporter assay identified that miR-27a/b directly regulates the expression of PPARγ in PASMC. Further study indicated that the presence of either NF-κB inhibitor pyrrolidinedithiocarbamate or prior silencing miR-27a/b with anti-miRNA oligonucleotides suppressed ET-1-induced PPARγ reduction and proliferation of PASMC, while overexpression of miR-27a/b reduced PPARγ expression and enhanced PASMC proliferation. Taken together, our study demonstrates that ET-1 stimulates miR-27a/b expression by activation of the NF-κB pathway, which in turn results in PPARγ reduction and contributes to ET-1-induced PASMC proliferation.
AB - The down-regulation of peroxisome proliferator-activated receptor γ (PPARγ) expression has been found to correlate with the proliferation of pulmonary artery smooth muscle cells (PASMC), pulmonary vascular remodeling and pulmonary hypertension, while the molecular mechanisms underlying PPARγ reduction in PASMC remain largely unclear. The aim of the current study is to address this issue. Endothelin-1 (ET-1) dose- and time-dependently resulted in PPARγ reduction and proliferation of primary cultured rat PASMC, which was accompanied by the activation of nuclear factor-kappaB (NF-κB) and subsequent induction of microRNA-27a/b (miR-27a/b) expression. Chromatin immunoprecipitation assay revealed that NF-κB directly bound to the promoter regions of miR-27a/b. Luciferase reporter assay identified that miR-27a/b directly regulates the expression of PPARγ in PASMC. Further study indicated that the presence of either NF-κB inhibitor pyrrolidinedithiocarbamate or prior silencing miR-27a/b with anti-miRNA oligonucleotides suppressed ET-1-induced PPARγ reduction and proliferation of PASMC, while overexpression of miR-27a/b reduced PPARγ expression and enhanced PASMC proliferation. Taken together, our study demonstrates that ET-1 stimulates miR-27a/b expression by activation of the NF-κB pathway, which in turn results in PPARγ reduction and contributes to ET-1-induced PASMC proliferation.
KW - Endothelin-1
KW - Nuclear factor-kappaB
KW - Peroxisome proliferator-activated receptor γ
KW - Pulmonary artery smooth muscle cells
KW - Pulmonary hypertension
KW - miR-27a/b
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U2 - 10.1007/s00441-017-2625-9
DO - 10.1007/s00441-017-2625-9
M3 - Article
C2 - 28484848
AN - SCOPUS:85019017900
SN - 0302-766X
VL - 369
SP - 527
EP - 539
JO - Cell and Tissue Research
JF - Cell and Tissue Research
IS - 3
ER -