Bortezomib Inhibits Lung Fibrosis and Fibroblast Activation without Proteasome Inhibition.

ABSTRACT: The U.S. Food and Drug Administration-approved proteasomal inhibitor bortezomib (BTZ) has attracted interest for its potential antifibrotic actions. However, neither its in vivo efficacy in lung fibrosis nor its dependence on proteasome inhibition has been conclusively defined. In this study, we assessed the therapeutic efficacy of BTZ in a mouse model of pulmonary fibrosis, developed an in vitro protocol to define its actions on diverse fibroblast activation parameters, determined its reliance on proteasome inhibition for these actions in vivo and in vitro, and explored alternative mechanisms of action. The therapeutic administration of BTZ diminished the severity of pulmonary fibrosis without reducing proteasome activity in the lung. In experiments designed to

SUBMITTER: Penke LRK 

PROVIDER: S-EPMC8803353 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature