Cargando…

Identification of Novel Therapeutic Targets for Pulmonary Arterial Hypertension

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Satoh, Kimio, Kikuchi, Nobuhiro, Satoh, Taijyu, Kurosawa, Ryo, Sunamura, Shinichiro, Siddique, Mohammad Abdul Hai, Omura, Junichi, Yaoita, Nobuhiro, Shimokawa, Hiroaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321293/
https://www.ncbi.nlm.nih.gov/pubmed/30562953
http://dx.doi.org/10.3390/ijms19124081
_version_ 1783385407536234496
author Satoh, Kimio
Kikuchi, Nobuhiro
Satoh, Taijyu
Kurosawa, Ryo
Sunamura, Shinichiro
Siddique, Mohammad Abdul Hai
Omura, Junichi
Yaoita, Nobuhiro
Shimokawa, Hiroaki
author_facet Satoh, Kimio
Kikuchi, Nobuhiro
Satoh, Taijyu
Kurosawa, Ryo
Sunamura, Shinichiro
Siddique, Mohammad Abdul Hai
Omura, Junichi
Yaoita, Nobuhiro
Shimokawa, Hiroaki
author_sort Satoh, Kimio
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6321293
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-63212932019-01-07 Identification of Novel Therapeutic Targets for Pulmonary Arterial Hypertension Satoh, Kimio Kikuchi, Nobuhiro Satoh, Taijyu Kurosawa, Ryo Sunamura, Shinichiro Siddique, Mohammad Abdul Hai Omura, Junichi Yaoita, Nobuhiro Shimokawa, Hiroaki Int J Mol Sci Review 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. MDPI 2018-12-17 /pmc/articles/PMC6321293/ /pubmed/30562953 http://dx.doi.org/10.3390/ijms19124081 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Satoh, Kimio
Kikuchi, Nobuhiro
Satoh, Taijyu
Kurosawa, Ryo
Sunamura, Shinichiro
Siddique, Mohammad Abdul Hai
Omura, Junichi
Yaoita, Nobuhiro
Shimokawa, Hiroaki
Identification of Novel Therapeutic Targets for Pulmonary Arterial Hypertension
title Identification of Novel Therapeutic Targets for Pulmonary Arterial Hypertension
title_full Identification of Novel Therapeutic Targets for Pulmonary Arterial Hypertension
title_fullStr Identification of Novel Therapeutic Targets for Pulmonary Arterial Hypertension
title_full_unstemmed Identification of Novel Therapeutic Targets for Pulmonary Arterial Hypertension
title_short Identification of Novel Therapeutic Targets for Pulmonary Arterial Hypertension
title_sort identification of novel therapeutic targets for pulmonary arterial hypertension
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321293/
https://www.ncbi.nlm.nih.gov/pubmed/30562953
http://dx.doi.org/10.3390/ijms19124081
work_keys_str_mv AT satohkimio identificationofnoveltherapeutictargetsforpulmonaryarterialhypertension
AT kikuchinobuhiro identificationofnoveltherapeutictargetsforpulmonaryarterialhypertension
AT satohtaijyu identificationofnoveltherapeutictargetsforpulmonaryarterialhypertension
AT kurosawaryo identificationofnoveltherapeutictargetsforpulmonaryarterialhypertension
AT sunamurashinichiro identificationofnoveltherapeutictargetsforpulmonaryarterialhypertension
AT siddiquemohammadabdulhai identificationofnoveltherapeutictargetsforpulmonaryarterialhypertension
AT omurajunichi identificationofnoveltherapeutictargetsforpulmonaryarterialhypertension
AT yaoitanobuhiro identificationofnoveltherapeutictargetsforpulmonaryarterialhypertension
AT shimokawahiroaki identificationofnoveltherapeutictargetsforpulmonaryarterialhypertension