2. Academic Validation
  3. Proteasome inhibitor bortezomib prevents proliferation and migration of pulmonary arterial smooth muscle cells

Proteasome inhibitor bortezomib prevents proliferation and migration of pulmonary arterial smooth muscle cells

  • Kaohsiung J Med Sci. 2024 Apr 29. doi: 10.1002/kjm2.12835.
Yi-Ching Liu 1,  Yu-Hsin Tseng 1,  Yu-Hsin Kuan 2,  Lin-Yen Wang 3 4 5 6,  Shang-En Huang 7,  Siao-Ping Tsai 8,  Jwu-Lai Yeh 7 9 10 11,  Jong-Hau Hsu 1 8
Affiliations

Affiliations

  • 1 Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 2 Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
  • 3 Department of Pediatrics, Chi-Mei Medical Center, Tainan, Taiwan.
  • 4 School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan.
  • 5 School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 6 Department of Childhood Education and Nursery, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
  • 7 Department of Pharmacology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 8 Department of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 9 Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
  • 10 Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 11 Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan.
PMID: 38682650 DOI: 10.1002/kjm2.12835
Abstract

Pulmonary vascular remodeling is a key pathological process of pulmonary arterial hypertension (PAH), characterized by uncontrolled proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs). Bortezomib (BTZ) is the first Food and Drug Administration (FDA)-approved Proteasome Inhibitor for multiple myeloma treatment. Recently, there is emerging evidence showing its effect on reversing PAH, although its mechanisms are not well understood. In this study, anti-proliferative and anti-migratory effects of BTZ on PASMCs were first examined by different inducers such as fetal bovine serum (FBS), angiotensin II (Ang II) and platelet-derived growth factor (PDGF)-BB, while potential mechanisms including cellular Reactive Oxygen Species (ROS) and mitochondrial ROS were then investigated; finally, signal transduction of ERK and Akt was examined. Our results showed that BTZ attenuated FBS-, Ang II- and PDGF-BB-induced proliferation and migration, with associated decreased cellular ROS production and mitochondrial ROS production. In addition, the phosphorylation of ERK and Akt induced by Ang II and PDGF-BB was also inhibited by BTZ treatment. This study indicates that BTZ can prevent proliferation and migration of PASMCs, which are possibly mediated by decreased ROS production and down-regulation of ERK and Akt. Thus, Proteasome inhibition can be a novel pharmacological target in the management of PAH.

Keywords

bortezomib; migration; proliferation; pulmonary arterial hypertension.

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