PMID- 31634459
OWN - NLM
STAT- MEDLINE
DCOM- 20200422
LR  - 20221207
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 865
DP  - 2019 Dec 15
TI  - Matrine pre-treatment suppresses AGEs- induced HCSMCs fibrotic responses by 
      regulating Poldip2/mTOR pathway.
PG  - 172746
LID - S0014-2999(19)30698-3 [pii]
LID - 10.1016/j.ejphar.2019.172746 [doi]
AB  - The fibrotic response of vascular smooth muscle cells (VSMCs) takes 
      responsibilities in atherosclerosis. Advanced glycation end products (AGEs) 
      induce and promote the fibrotic responses of VSMCs. Matrine shows potent 
      anti-fibrotic and cardio-protective effects. This study was aimed to investigate 
      the underlying mechanisms of matrine's inhibitory effects on AGEs-induced VSMCs 
      fibrotic responses. Cultured human coronary smooth muscle cells (HCSMCs) were 
      pre-treated with matrine and exposed to AGEs. Specific siRNA was used to silence 
      polymerase delta interacting protein 2 (Poldip2) expression. Sircol collagen 
      assay was used to assess collagen content. Protein expression and phosphorylation 
      levels were determined by Western blotting. Matrine pre-treatment significantly 
      reduced collagen content, increased smooth muscle myosin heavy chain 11 (MYH11) 
      and Poldip2 expression, decreased expressions of collagen I, beta1-integrin, 
      phsphoinositide-3-kinase (PI3K) and nuclear phosphorylated p70S6k, and reduced 
      phosphorylation levels of protein kinase B (Akt) and mechanistic target of 
      rapamycin (mTOR) in HCSMCs exposed to AGEs in a concentration dependent manner. 
      Specific siRNA effectively silenced Poldip2 expression and impaired matrine's 
      effect on collagen content, expressions of MYH11, collagen I, beta1-integrin, PI3K, 
      nuclear p-p70S6k and phosphorylation levels of Akt and mTOR in HCSMCs exposed to 
      AGEs. Matrine suppresses AGEs- induced fibrotic responses in HCSMCs via 
      regulating Poldip2/mTOR signaling pathway.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Ma, Wangxia
AU  - Ma W
AD  - Department of Cardiology, The First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an, Shaanxi Province, China; Department of Cardiology, Shaanxi 
      Provincial People's Hospital, Xi'an, Shaanxi Province, China; Department of 
      Cardiology, Zhouzhi County People's Hospital, Xi'an, Shaanxi Province, China.
FAU - Xu, Jing
AU  - Xu J
AD  - Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 
      Province, China.
FAU - Zhang, Yong
AU  - Zhang Y
AD  - Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 
      Province, China.
FAU - Zhang, Hong
AU  - Zhang H
AD  - Department of Cardiology, The First Affiliated Hospital of Baotou Medical 
      College, Baotou, the Nei Monggol Autonomous Region, China.
FAU - Zhang, Zhu
AU  - Zhang Z
AD  - Department of Cardiology, The First Affiliated Hospital of Baotou Medical 
      College, Baotou, the Nei Monggol Autonomous Region, China.
FAU - Zhou, Liqin
AU  - Zhou L
AD  - Department of Cardiology, The First Affiliated Hospital of Baotou Medical 
      College, Baotou, the Nei Monggol Autonomous Region, China.
FAU - Wang, Xincheng
AU  - Wang X
AD  - Department of Cardiology, Zhouzhi County People's Hospital, Xi'an, Shaanxi 
      Province, China.
FAU - Liu, Hongbo
AU  - Liu H
AD  - Department of Cardiology, Zhouzhi County People's Hospital, Xi'an, Shaanxi 
      Province, China.
FAU - Chen, Yani
AU  - Chen Y
AD  - Department of Cardiology, Zhouzhi County People's Hospital, Xi'an, Shaanxi 
      Province, China.
FAU - Du, Peng
AU  - Du P
AD  - Department of Cardiology, Zhouzhi County People's Hospital, Xi'an, Shaanxi 
      Province, China.
FAU - Min, Ningbin
AU  - Min N
AD  - Department of Cardiology, Heyang County People's Hospital, Weinan, Shaanxi 
      Province, China. Electronic address: qiangzhui304@163.com.
FAU - Liu, Zhongwei
AU  - Liu Z
AD  - Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 
      Province, China. Electronic address: liuzhongwei@xjtu.edu.cn.
FAU - Yin, Yanrong
AU  - Yin Y
AD  - Department of Cardiology, The First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an, Shaanxi Province, China. Electronic address: yronger@163.com.
LA  - eng
PT  - Journal Article
DEP - 20191018
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Alkaloids)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Nuclear Proteins)
RN  - 0 (POLDIP2 protein, human)
RN  - 0 (Quinolizines)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 0 (Matrines)
SB  - IM
MH  - Alkaloids/*pharmacology
MH  - Coronary Vessels/*pathology
MH  - Fibrosis
MH  - Glycation End Products, Advanced/antagonists & inhibitors/*pharmacology
MH  - Humans
MH  - Myocytes, Smooth Muscle/*drug effects/metabolism/*pathology
MH  - Nuclear Proteins/*metabolism
MH  - Quinolizines/*pharmacology
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Matrines
OTO - NOTNLM
OT  - Advanced glycation end products
OT  - Fibrosis
OT  - Matrine
OT  - Poldip2
OT  - Vascular smooth muscle cells
OT  - mTOR signaling pathway
EDAT- 2019/10/22 06:00
MHDA- 2020/04/23 06:00
CRDT- 2019/10/22 06:00
PHST- 2019/08/27 00:00 [received]
PHST- 2019/10/15 00:00 [revised]
PHST- 2019/10/17 00:00 [accepted]
PHST- 2019/10/22 06:00 [pubmed]
PHST- 2020/04/23 06:00 [medline]
PHST- 2019/10/22 06:00 [entrez]
AID - S0014-2999(19)30698-3 [pii]
AID - 10.1016/j.ejphar.2019.172746 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2019 Dec 15;865:172746. doi: 10.1016/j.ejphar.2019.172746. Epub 
      2019 Oct 18.