Bone morphogenetic protein signalling in pulmonary hypertension: advances and therapeutic implications

Exp Physiol. 2017 Sep 1;102(9):1083-1089. doi: 10.1113/EP086041. Epub 2017 Jun 6.

Abstract

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.

Keywords: bone morphogenetic protein; pulmonary arterial smooth muscle; pulmonary hypertension.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein Receptors / metabolism
  • Bone Morphogenetic Proteins / metabolism*
  • Humans
  • Hypertension, Pulmonary / metabolism*
  • Ligands
  • Signal Transduction / physiology*

Substances

  • Bone Morphogenetic Proteins
  • Ligands
  • Bone Morphogenetic Protein Receptors