Why the study?
CAV1 and Cavin-1 regulate caveolae composition, and both CAV1 and BMPR2 are implicated in pulmonary arterial hypertension, but how their interactions influence BMP/Smad signaling is unclear.
The Cavin-1/Caveolin-1 interaction attenuates BMP/Smad signaling, and its inhibition via Cavin-1 knockdown reverses pulmonary hypertension in preclinical models, highlighting a novel therapeutic target for PAH.
No change to PAH care indicated; leaves open CAV1-BMPR2 links in human disease.
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 enhanced the CAV1/Cavin-1 interaction but attenuated 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 decreased BMPR2 membrane localization by inhibiting the interaction of BMPR2 with CAV1 and reduced Smad signal transduction in PAECs. Furthermore, Cavin-1 knockdown was resistant to CAV1-induced pulmonary hypertension in vivo. We demonstrated that the Cavin-1/Caveolin-1 interaction attenuates BMP/Smad signaling and is a promising target for the treatment of PAH.
No takes yet. Share an insight, caveat, or question.
Tomita et al. (2023) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: