scholarly journals Lipocalin-2 Promotes Endoplasmic Reticulum Stress and Proliferation by Augmenting Intracellular Iron in Human Pulmonary Arterial Smooth Muscle Cells

2017 ◽  
Vol 13 (2) ◽  
pp. 135-144 ◽  
Author(s):  
Guoliang Wang ◽  
Shenghua Liu ◽  
Li Wang ◽  
Liukun Meng ◽  
Chuanjue Cui ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Smooth Muscle ◽  
Endoplasmic Reticulum Stress ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Lipocalin 2 ◽  
Intracellular Iron ◽  
Pulmonary Arterial ◽  
Arterial Smooth Muscle Cells ◽  
Pulmonary Arterial Smooth Muscle

scholarly journals EXPRESS: Ubiquitin‑specific protease 7 mediates platelet derived growth factor-induced pulmonary arterial smooth muscle cells proliferation

2021 ◽  
pp. 204589402110461
Author(s):  
Yanting Zhu ◽  
Qianqian Zhang ◽  
Xin Yan ◽  
Lu Liu ◽  
Cui Zhai ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Platelet Derived Growth Factor ◽  
Specific Protease ◽  
Pulmonary Arterial ◽  
Arterial Smooth Muscle Cells ◽  
Pulmonary Arterial Smooth Muscle

Pulmonary arterial hypertension (PAH) 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 PAH. 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.

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