A review of BMP and Wnt signaling pathway in the pathogenesis of pulmonary arterial hypertension

ABSTRACT

Pulmonary arterial hypertension (PAH) is a chronic disease characterized by a progressive elevation in mean pulmonary arterial pressure. This occurs due to abnormal remodeling of small peripheral lung vasculature resulting in progressive occlusion of the artery lumen that eventually causes right heart failure and death. Current therapeutic options for PAH are limited and focused mainly on reversal of pulmonary vasoconstriction and proliferation of vascular cells. Although these treatments can relieve disease symptoms, PAH remains a progressive lethal disease.

Bone morphogenetic proteins (BMPs) and their receptors were required for PAH-induced right ventricular hypertrophy. Emerging data suggest that restoration of BMP type II receptor (BMPR2) signaling in PAH is a promising alternative that could prevent and reverse pulmonary vascular remodeling. BMPR2 mutations have been identified in >70% of familial and roughly 15% of sporadic PAH cases. Wingless (Wnt) are a family of secreted glycoproteins with varying expression patterns and a range of functions, Wnt signaling pathway is divided into canonical signaling pathway and non-canonical signaling pathway. A recent study reports that interaction between BMP and Wnt closely associated with lung development, those cascade coordination regulation stem cell fate which determine lung branching morphogenes. The promoting effect of BMPR2 on proliferation, survival, and motility of endothelial cells was through recruiting Wnts signaling pathway, the interaction between BMP and Wnt closely associated with lung development.

Therefore, in this review, we outline the latest advances of BMP and Wnt signaling pathway in the pathogenesis of PAH and disease progression.

KEYWORDS:

• PAH
• BMP
• Wnt5A
• PASMCs
• right ventricular failure

Acknowledgments

The authors are grateful to the Central Research Laboratory of the Second Hospital of Shandong University for technical assistance and generous support.

Disclosure statement

The authors declare that they have no competing interests.

Availability of supporting data

All data generated in this study are included in this manuscript.

Ethical Approval and Consent to participate

All participants were provided with written informed consent at the time of recruitment. This study was approved by the Ethics Committee of the Second Hospital of Shandong University.

Additional information

Funding

This project was supported by Natural Science Foundation of Shandong Province (ZR2020MH001), the Science and Technology Development Project of Jinan Medical and Health (202019126, 202019097 and 201907001), Science and Technology Development Project of Shandong Province (2019GSF107093).