PMID- 34552711
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210925
IS  - 2045-8932 (Print)
IS  - 2045-8940 (Electronic)
IS  - 2045-8932 (Linking)
VI  - 11
IP  - 4
DP  - 2021 Oct-Dec
TI  - Ubiquitin-specific protease 7 mediates platelet-derived growth factor-induced 
      pulmonary arterial smooth muscle cells proliferation.
PG  - 20458940211046131
LID - 10.1177/20458940211046131 [doi]
LID - 20458940211046131
AB  - Pulmonary arterial hypertension is a devastating pulmonary vascular disease, in 
      which the pathogenesis is complicated and unclear. Pulmonary arterial smooth 
      muscle cells (PASMCs) proliferation is a key pathological feature of pulmonary 
      arterial hypertension. It has been shown that ubiquitin-specific protease 7 
      (USP7) is involved in cancer cell proliferation via deubiquitinating and 
      stabilizing E3 ubiquitin ligase mouse double minute 2 (MDM2). However, the effect 
      of USP7 and MDM2 on platelet-derived growth factor (PDGF)-induced PASMCs 
      proliferation is uncertain. This study aims to explore this issue. Our results 
      indicated that PDGF up-regulated USP7 protein expression and stimulated PASMCs 
      proliferation; this was accompanied with the increase of MDM2, forkhead box O4 
      (FoxO4) reduction and elevation of CyclinD1. While prior transfection of USP7 
      siRNA blocked PDGF-induced MDM2 up-regulation, FoxO4 down-regulation, increase of 
      CyclinD1 and cell proliferation. Pre-depletion of MDM2 by siRNA transfection 
      reversed PDGF-induced reduction of FoxO4, up-regulation of CyclinD1 and PASMCs 
      proliferation. Furthermore, pre-treatment of cells with proteasome inhibitor 
      MG-132 also abolished PDGF-induced FoxO4 reduction, CyclinD1 elevation and cell 
      proliferation. Our study suggests that USP7 up-regulates MDM2, which facilitates 
      FoxO4 ubiquitinated degradation, and subsequently increases the expression of 
      CyclinD1 to mediate PDGF-induced PASMCs proliferation.
CI  - (c) The Author(s) 2021.
FAU - Zhu, Yanting
AU  - Zhu Y
AD  - Department of Respiratory Medicine, the First Affiliated Hospital of Xi'an Jiao 
      Tong University, Xi'an, People's Republic of China.
AD  - Center of Nephropathy and Hemodialysis, Shaanxi Provincial People's Hospital, 
      Xi'an, People's Republic of China.
FAU - Zhang, Qianqian
AU  - Zhang Q
AD  - Department of Respiratory Medicine, the First Affiliated Hospital of Xi'an Jiao 
      Tong University, Xi'an, People's Republic of China.
FAU - Yan, Xin
AU  - Yan X
AD  - Department of Respiratory Medicine, the First Affiliated Hospital of Xi'an Jiao 
      Tong University, Xi'an, People's Republic of China.
FAU - Liu, Lu
AU  - Liu L
AD  - Department of Respiratory Medicine, the First Affiliated Hospital of Xi'an Jiao 
      Tong University, Xi'an, People's Republic of China.
FAU - Zhai, Cui
AU  - Zhai C
AD  - Department of Respiratory Medicine, the First Affiliated Hospital of Xi'an Jiao 
      Tong University, Xi'an, People's Republic of China.
FAU - Wang, Qingting
AU  - Wang Q
AD  - Department of Respiratory Medicine, the First Affiliated Hospital of Xi'an Jiao 
      Tong University, Xi'an, People's Republic of China.
FAU - Chai, Limin
AU  - Chai L
AD  - Department of Respiratory Medicine, the First Affiliated Hospital of Xi'an Jiao 
      Tong University, Xi'an, People's Republic of China.
FAU - Li, Manxiang
AU  - Li M
AUID- ORCID: 0000-0003-1539-3102
AD  - Department of Respiratory Medicine, the First Affiliated Hospital of Xi'an Jiao 
      Tong University, Xi'an, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20210916
PL  - United States
TA  - Pulm Circ
JT  - Pulmonary circulation
JID - 101557243
PMC - PMC8451001
OTO - NOTNLM
OT  - forkhead box O4 (FoxO4)
OT  - mouse double minute 2 (MDM2)
OT  - proliferation
OT  - pulmonary arterial smooth muscle cells
OT  - ubiquitin-specific protease 7 (USP7)
EDAT- 2021/09/24 06:00
MHDA- 2021/09/24 06:01
PMCR- 2021/09/16
CRDT- 2021/09/23 06:51
PHST- 2020/12/31 00:00 [received]
PHST- 2021/08/25 00:00 [accepted]
PHST- 2021/09/23 06:51 [entrez]
PHST- 2021/09/24 06:00 [pubmed]
PHST- 2021/09/24 06:01 [medline]
PHST- 2021/09/16 00:00 [pmc-release]
AID - 10.1177_20458940211046131 [pii]
AID - 10.1177/20458940211046131 [doi]
PST - epublish
SO  - Pulm Circ. 2021 Sep 16;11(4):20458940211046131. doi: 10.1177/20458940211046131. 
      eCollection 2021 Oct-Dec.