Estrogen and Cyp1b1 Regulate Pparγ in Pulmonary Hypertension Through a Ubiquitin-Dependent Mechanism.

ABSTRACT: Female sex increases risk of Group I pulmonary arterial hypertension by roughly threefold, but the mechanism is unclear. Low expression of Cyp1b1, an enzyme that metabolizes estrogens, is associated with disease penetrance, particularly in women. We previously found that lower Pparγ levels in murine PAH models, which may drive disease, are rescued by estrogen blockade. The goal of the current studies was to examine interaction of estrogen, Cyp1b1, and energy metabolism in cell culture and in knockout mice. We found that both estrogen and siRNA to Cyp1b1 resulted in reduction of Pparγ at a protein, but not transcript level, in addition to regulating Pparγ cofactors. siCyp1b1 reduced both basal and maximal respiration rates in a fatty acid oxidation Seahorse protocol. This Pparγ inhibition c

SUBMITTER: Chen J 

PROVIDER: S-EPMC11825585 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature