PMID- 29943847
OWN - NLM
STAT- MEDLINE
DCOM- 20191009
LR  - 20210821
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 119
IP  - 10
DP  - 2018 Nov
TI  - Pathological cyclic strain promotes proliferation of vascular smooth muscle cells 
      via the ACTH/ERK/STAT3 pathway.
PG  - 8260-8270
LID - 10.1002/jcb.26839 [doi]
AB  - Abnormal proliferation of vascular smooth muscle cells (VSMCs) is closely related 
      to hyperplasia in hypertension. Our previous study suggested that 
      adrenocorticotropic hormone (ACTH) is mechano-responsive and may regulate VSMC 
      proliferation. However, the molecular mechanism of VSMC abnormal proliferation 
      induced by conditions of high cyclic strain, especially the role of ACTH in this 
      process, is unclear. Our results revealed that ACTH and its specific receptor 
      melanocortin receptor type 2 (MC2R) were highly expressed in hypertensive rat 
      models. Furthermore, it was demonstrated that the expression of ACTH and MC2R was 
      up-regulated when exposed to high cyclic strain in vitro, accompanied by abnormal 
      proliferation of VSMCs. Next, it was proved that ACTH-dependent cell 
      proliferation was related to the phosphorylation of extracellular regulated 
      protein kinases (ERK) and signal transducer and activator of transcription 3 
      (STAT3). The study also found that ACTH could promote dimerization and 
      glycosylation of melanocortin 2 receptor accessory protein (MRAP), which had a 
      significant effect on MC2R membrane localization and signal activation. When 
      VSMCs were treated with PD98059, a mitogen-activated protein kinase (MAP kinase) 
      cascade antagonist, it was determined that phosphorylation of STAT3 at Ser727 was 
      dependent on ERK phosphorylation. In summary, these data demonstrated that the 
      abnormal proliferation of VSMCs induced by conditions of high cyclic strain is in 
      part attributed to ACTH and its receptor MC2R. Identifying the mechanism of 
      ACTH-dependent proliferation of VSMCs may help to provide new therapeutic targets 
      for hypertension.
CI  - (c) 2018 Wiley Periodicals, Inc.
FAU - Tang, Xia
AU  - Tang X
AD  - Institute of Mechanobiology and Medical Engineering, School of Life Sciences and 
      Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
FAU - Liu, Yanyan
AU  - Liu Y
AD  - Institute of Mechanobiology and Medical Engineering, School of Life Sciences and 
      Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
FAU - Xiao, Qian
AU  - Xiao Q
AD  - Institute of Mechanobiology and Medical Engineering, School of Life Sciences and 
      Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
FAU - Yao, Qingping
AU  - Yao Q
AD  - Institute of Mechanobiology and Medical Engineering, School of Life Sciences and 
      Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
FAU - Allen, Molly
AU  - Allen M
AD  - Department of Bioengineering, University of California, San Diego, California.
FAU - Wang, Yingxiao
AU  - Wang Y
AD  - Department of Bioengineering, University of California, San Diego, California.
FAU - Gao, Lizhi
AU  - Gao L
AD  - Institute of Mechanobiology and Medical Engineering, School of Life Sciences and 
      Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
FAU - Qi, Yingxin
AU  - Qi Y
AD  - Institute of Mechanobiology and Medical Engineering, School of Life Sciences and 
      Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
FAU - Zhang, Ping
AU  - Zhang P
AUID- ORCID: 0000-0002-4873-4383
AD  - Institute of Mechanobiology and Medical Engineering, School of Life Sciences and 
      Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
AD  - National Experimental Teaching Demonstration of Life Sciences and Biotechnology, 
      Shanghai Jiao Tong University, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180626
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Flavonoids)
RN  - 0 (Receptor, Melanocortin, Type 2)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, rat)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Adrenocorticotropic Hormone/*genetics/metabolism
MH  - Animals
MH  - Biomechanical Phenomena
MH  - Cell Proliferation/drug effects
MH  - Disease Models, Animal
MH  - Female
MH  - Flavonoids/pharmacology
MH  - Gene Expression Regulation
MH  - Hypertension/*genetics/metabolism/physiopathology
MH  - *Mechanotransduction, Cellular
MH  - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/genetics/metabolism
MH  - Mitogen-Activated Protein Kinase 3/genetics/metabolism
MH  - Muscle, Smooth, Vascular/metabolism/pathology
MH  - Myocytes, Smooth Muscle/drug effects/*metabolism/pathology
MH  - Phosphorylation/drug effects
MH  - Pregnancy
MH  - Primary Cell Culture
MH  - Rats
MH  - Receptor, Melanocortin, Type 2/*genetics/metabolism
MH  - STAT3 Transcription Factor/*genetics/metabolism
MH  - Stress, Mechanical
OTO - NOTNLM
OT  - ACTH
OT  - ERK
OT  - STAT3
OT  - VSMC
OT  - cyclic strain
OT  - proliferation
EDAT- 2018/06/27 06:00
MHDA- 2019/10/11 06:00
CRDT- 2018/06/27 06:00
PHST- 2017/11/20 00:00 [received]
PHST- 2018/03/09 00:00 [accepted]
PHST- 2018/06/27 06:00 [pubmed]
PHST- 2019/10/11 06:00 [medline]
PHST- 2018/06/27 06:00 [entrez]
AID - 10.1002/jcb.26839 [doi]
PST - ppublish
SO  - J Cell Biochem. 2018 Nov;119(10):8260-8270. doi: 10.1002/jcb.26839. Epub 2018 Jun 
      26.