Yang Kai, Wang Jian, Lu Wenju
State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.
Exp Physiol. 2017 Sep 1;102(9):1083-1089. doi: 10.1113/EP086041. Epub 2017 Jun 6.
What is the topic of this review? This review covers recent evidence highlighting the crucial pathophysiological roles and molecular mechanisms of the bone morphogenetic protein (BMP) signalling pathway during the progression of pulmonary hypertension (PH) and discusses targeting of BMP signalling as a new treatment option against PH. What advances does it highlight? A series of breakthrough findings have greatly enriched our understanding about the mechanism of action of BMP signalling in PH and proved the feasibility of BMP targeting strategies in experimental PH models. This review collects these ideas and discusses the frontiers of BMP signalling-targeted PH therapy at different steps of the signal transduction. The bone morphogenetic protein (BMP)-mediated signalling pathway plays crucial roles in the development and progression of pulmonary hypertension (PH). Typical BMP signalling involves BMP ligands, specific transmembrane serine/threonine kinase receptors, cellular responsive kinases and secreted antagonists. As more and more studies have been conducted, the specific protective or pathogenic roles of these molecules within all these subgroups of BMP signalling have been continuously uncovered. Based on this evidence, specific strategies have been designed by targeting these factors as a new treatment approach to PH. In this review, we have collected recent advances in the exciting findings that link BMP signalling with the pathogenesis of PH and we discuss the potential future frontiers in therapeutic design.
本综述的主题是什么？本综述涵盖了近期的证据，这些证据突出了骨形态发生蛋白（BMP）信号通路在肺动脉高压（PH）进展过程中的关键病理生理作用和分子机制，并讨论了将BMP信号作为抗PH的新治疗选择进行靶向治疗。它突出了哪些进展？一系列突破性发现极大地丰富了我们对BMP信号在PH中的作用机制的理解，并证明了BMP靶向策略在实验性PH模型中的可行性。本综述收集了这些观点，并在信号转导的不同步骤讨论了以BMP信号为靶点的PH治疗的前沿问题。骨形态发生蛋白（BMP）介导的信号通路在肺动脉高压（PH）的发生和发展中起关键作用。典型的BMP信号涉及BMP配体、特定的跨膜丝氨酸/苏氨酸激酶受体、细胞反应性激酶和分泌性拮抗剂。随着越来越多的研究开展，这些分子在BMP信号所有这些亚组中的具体保护或致病作用不断被揭示。基于这些证据，通过靶向这些因子设计了特定策略，作为PH的一种新治疗方法。在本综述中，我们收集了将BMP信号与PH发病机制联系起来的令人兴奋的发现的近期进展，并讨论了治疗设计中潜在的未来前沿问题。
