Identification of novel therapeutic targets for pulmonary arterial hypertension

Kimio Satoh, Nobuhiro Kikuchi, Taijyu Satoh, Ryo Kurosawa, Shinichiro Sunamura, Mohammad Abdul Hai Siddique, Junichi Omura, Nobuhiro Yaoita, Hiroaki Shimokawa

Research output: Contribution to journalReview articlepeer-review

6 Citations (Scopus)

Abstract

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are fatal diseases; however, their pathogenesis still remains to be elucidated. We have recently screened novel pathogenic molecules and have performed drug discovery targeting those molecules. Pulmonary artery smooth muscle cells (PASMCs) in patients with PAH (PAH-PASMCs) have high proliferative properties like cancer cells, which leads to thickening and narrowing of distal pulmonary arteries. Thus, we conducted a comprehensive analysis of PAH-PASMCs and lung tissues to search for novel pathogenic proteins. We validated the pathogenic role of the selected proteins by using tissue-specific knockout mice. To confirm its clinical significance, we used patient-derived blood samples to evaluate the potential as a biomarker for diagnosis and prognosis. Finally, we conducted a high throughput screening and found inhibitors for the pathogenic proteins.

Original languageEnglish
Article number4081
JournalInternational journal of molecular sciences
Volume19
Issue number12
DOIs
Publication statusPublished - 2018

Keywords

  • Biomarker
  • Drug discovery
  • Pathogenesis
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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