The sonic hedgehog signaling inhibitor cyclopamine improves pulmonary arterial hypertension via regulating the bone morphogenetic protein receptor 2 pathway.

ABSTRACT: Pulmonary arterial hypertension (PAH) is a severe and progressive disease with hallmarks of pulmonary vascular remodeling and bone morphogenetic protein receptor 2 (BMPR2) mutation. Recent studies indicate Sonic hedgehog (SHH) signaling is involved in the proliferation of human pulmonary arterial smooth muscle cells (hPASMCs) but the role of the SHH signaling inhibitor cyclopamine in monocrotaline (MCT)-induced PAH has not been investigated. We hypothesized SHH promotes pulmonary vascular remodeling and that inhibition of SHH signaling by cyclopamine could attenuate pulmonary hypertension via the bone morphogenetic protein (BMP) pathway. SHH and BMPR2 proteins were measured in pulmonary arteries isolated from MCT-induced PAH rats and in hPASMCs. The therapeutic effects of cyclopamine were

SUBMITTER: Jin Y 

PROVIDER: S-EPMC11992095 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature