The Cavin-1/Caveolin-1 interaction attenuates BMP/Smad signaling in pulmonary hypertension by interfering with BMPR2/Caveolin-1 binding

Commun Biol. 2024 Jan 5;7(1):40. doi: 10.1038/s42003-023-05693-2.

Abstract

Caveolin-1 (CAV1) and Cavin-1 are components of caveolae, both of which interact with and influence the composition and stabilization of caveolae. CAV1 is associated with pulmonary arterial hypertension (PAH). Bone morphogenetic protein (BMP) type 2 receptor (BMPR2) is localized in caveolae associated with CAV1 and is commonly mutated in PAH. Here, we show that BMP/Smad signaling is suppressed in pulmonary microvascular endothelial cells of CAV1 knockout mice. Moreover, hypoxia enhances the CAV1/Cavin-1 interaction but attenuates the CAV1/BMPR2 interaction and BMPR2 membrane localization in pulmonary artery endothelial cells (PAECs). Both Cavin-1 and BMPR2 are associated with the CAV1 scaffolding domain. Cavin-1 decreases BMPR2 membrane localization by inhibiting the interaction of BMPR2 with CAV1 and reduces Smad signal transduction in PAECs. Furthermore, Cavin-1 knockdown is resistant to CAV1-induced pulmonary hypertension in vivo. We demonstrate that the Cavin-1/Caveolin-1 interaction attenuates BMP/Smad signaling and is a promising target for the treatment of PAH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caveolin 1* / genetics
  • Caveolin 1* / metabolism
  • Endothelial Cells
  • Hypertension, Pulmonary*
  • Membrane Proteins* / genetics
  • Membrane Proteins* / metabolism
  • Mice
  • Mice, Knockout
  • Pulmonary Arterial Hypertension
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism
  • Signal Transduction*

Substances

  • Caveolin 1
  • Cav1 protein, mouse
  • Cavin1 protein, mouse
  • Membrane Proteins
  • RNA-Binding Proteins