PMID- 35410639
OWN - NLM
STAT- MEDLINE
DCOM- 20220603
LR  - 20220716
IS  - 1976-670X (Electronic)
IS  - 1976-6696 (Print)
IS  - 1976-6696 (Linking)
VI  - 55
IP  - 5
DP  - 2022 May
TI  - Inhibition of VRK1 suppresses proliferation and migration of vascular smooth 
      muscle cells and intima hyperplasia after injury via mTORC1/beta-catenin axis.
PG  - 244-249
AB  - Characterized by abnormal proliferation and migration of vascular smooth muscle 
      cells (VSMCs), neointima hyperplasia is a hallmark of vascular restenosis after 
      percutaneous vascular interventions. Vaccinia-related kinase 1 (VRK1) is a stress 
      adaptionassociated ser/thr protein kinase that can induce the proliferation of 
      various types of cells. However, the role of VRK1 in the proliferation and 
      migration of VSMCs and neointima hyperplasia after vascular injury remains 
      unknown. We observed increased expression of VRK1 in VSMCs subjected to 
      platelet-derived growth factor (PDGF)-BB by western blotting. Silencing VRK1 by 
      shVrk1 reduced the number of Ki-67-positive VSMCs and attenuated the migration of 
      VSMCs. Mechanistically, we found that relative expression levels of beta-catenin and 
      effectors of mTOR complex 1 (mTORC1) such as phospho (p)-mammalian target of 
      rapamycin (mTOR), p-S6, and p-4EBP1 were decreased after silencing VRK1. 
      Restoration of beta-catenin expression by SKL2001 and re-activation of mTORC1 by 
      Tuberous sclerosis 1 siRNA (siTsc1) both abolished shVrk1-mediated inhibitory 
      effect on VSMC proliferation and migration. siTsc1 also rescued the reduced 
      expression of beta-catenin caused by VRK1 inhibition. Furthermore, mTORC1 
      re-activation failed to recover the attenuated proliferation and migration of 
      VSMC resulting from shVrk1 after silencing beta-catenin. We also found that the 
      vascular expression of VRK1 was increased after injury. VRK1 inactivation in vivo 
      inhibited vascular injury-induced neointima hyperplasia in a beta-catenin-dependent 
      manner. These results demonstrate that inhibition of VRK1 can suppress the 
      proliferation and migration of VSMC and neointima hyperplasia after vascular 
      injury via mTORC1/beta-catenin pathway. [BMB Reports 2022; 55(5): 244-249].
FAU - Sun, Xiongshan
AU  - Sun X
AD  - Department of Cardiology, The General Hospital of Western Theater Command, 
      Chengdu 610083, China.
FAU - Zhao, Weiwei
AU  - Zhao W
AD  - Department of Cardiology, The General Hospital of Western Theater Command, 
      Chengdu 610083, China.
FAU - Wang, Qiang
AU  - Wang Q
AD  - Department of Cardiology, The General Hospital of Western Theater Command, 
      Chengdu 610083, China.
FAU - Zhao, Jiaqi
AU  - Zhao J
AD  - Department of Cardiology, The General Hospital of Western Theater Command, 
      Chengdu 610083, China.
FAU - Yang, Dachun
AU  - Yang D
AD  - Department of Cardiology, The General Hospital of Western Theater Command, 
      Chengdu 610083, China.
FAU - Yang, Yongjian
AU  - Yang Y
AD  - Department of Cardiology, The General Hospital of Western Theater Command, 
      Chengdu 610083, China.
LA  - eng
PT  - News
PL  - Korea (South)
TA  - BMB Rep
JT  - BMB reports
JID - 101465334
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (beta Catenin)
RN  - 1B56C968OA (Becaplermin)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (VRK1 protein, human)
SB  - IM
MH  - Becaplermin/pharmacology
MH  - Carotid Intima-Media Thickness
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Humans
MH  - Hyperplasia
MH  - *Intracellular Signaling Peptides and Proteins/antagonists & 
      inhibitors/metabolism
MH  - Mechanistic Target of Rapamycin Complex 1/metabolism
MH  - *Muscle, Smooth, Vascular/metabolism/pathology
MH  - Myocytes, Smooth Muscle/metabolism
MH  - *Neointima/metabolism/pathology
MH  - *Protein Serine-Threonine Kinases/antagonists & inhibitors/metabolism
MH  - Signal Transduction
MH  - *TOR Serine-Threonine Kinases/metabolism
MH  - *Vascular System Injuries/metabolism/pathology
MH  - *beta Catenin/metabolism
PMC - PMC9152580
COIS- CONFLICTS OF INTEREST The authors have no conflicting interests.
EDAT- 2022/04/13 06:00
MHDA- 2022/06/07 06:00
PMCR- 2022/05/31
CRDT- 2022/04/12 05:26
PHST- 2022/02/24 00:00 [received]
PHST- 2022/04/13 06:00 [pubmed]
PHST- 2022/06/07 06:00 [medline]
PHST- 2022/04/12 05:26 [entrez]
PHST- 2022/05/31 00:00 [pmc-release]
AID - 5570 [pii]
AID - bmb-55-5-244 [pii]
AID - 10.5483/BMBRep.2022.55.5.019 [doi]
PST - ppublish
SO  - BMB Rep. 2022 May;55(5):244-249. doi: 10.5483/BMBRep.2022.55.5.019.