期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 24, 期 16, 页码 -出版社
MDPI
DOI: 10.3390/ijms241612653
关键词
PDGFR; c-KIT; CSF1R; ABL; imatinib; dasatinib; inhalation
Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling and increased pulmonary vascular resistance. Histologically, PAH is characterized by plexiform and neointimal lesions composed of dysregulated endothelial cells and myofibroblasts. The PDGFR-CSF1R-c-KIT signaling network has been implicated in PAH pathogenesis, and inhibition of this network has potential therapeutic benefits. Seralutinib, which targets these pathways, shows promise for the treatment of PAH.
Pulmonary arterial hypertension (PAH) is a complex disorder characterized by vascular remodeling and a consequent increase in pulmonary vascular resistance. The histologic hallmarks of PAH include plexiform and neointimal lesions of the pulmonary arterioles, which are composed of dysregulated, apoptosis-resistant endothelial cells and myofibroblasts. Platelet-derived growth factor receptors (PDGFR) alpha and beta, colony stimulating factor 1 receptor (CSF1R), and mast/stem cell growth factor receptor kit (c-KIT) are closely related kinases that have been implicated in PAH progression. In addition, emerging data indicate significant crosstalk between PDGF signaling and the bone morphogenetic protein receptor type 2 (BMPR2)/transforming growth factor beta (TGF beta) receptor axis. This review will discuss the importance of the PDGFR-CSF1R-c-KIT signaling network in PAH pathogenesis, present evidence that the inhibition of all three nodes in this kinase network is a potential therapeutic approach for PAH, and highlight the therapeutic potential of seralutinib, currently in development for PAH, which targets these pathways.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据