Bnip3 regulates airway smooth muscle cell focal adhesion and proliferation.

Abstract

Increased airway smooth muscle (ASM) mass is a key contributor to airway narrowing and airway hyperresponsiveness in asthma. Besides conventional pathways and regulators of ASM proliferation, recent studies suggest that changes in mitochondrial morphology and function play a role in airway remodeling in asthma. In this study, we aimed at determining the role of mitochondrial Bcl-2 adenovirus E1B 19 kDa-interacting protein, Bnip3, in the regulation of ASM proliferation. Bnip3 is a member of the Bcl-2 family of proteins critical for mitochondrial health, mitophagy, and cell survival/death. We found that Bnip3 expression is upregulated in ASM cells from asthmatic donors compared with that in ASM cells from healthy donors and transient downregulation of Bnip3 expression in primary human ASM cells using an siRNA approach decreased cell adhesion, migration, and proliferation. Furthermore, Bnip3 downregulation altered the structure (electron density) and function (cellular ATP levels, membrane potential, and reacitve oxygen species generation) of mitochondria and decreased expression of cytoskeleton proteins vinculin, paxillin, and actinin. These findings suggest that Bnip3 via regulation of mitochondria functions and expression of adhesion proteins regulates ASM adhesion, migration, and proliferation. This study reveals a novel role for Bnip3 in ASM functions and establishes Bnip3 as a potential target in mitigating ASM remodeling in asthma.