Sustained Activation of Rho GTPases Promotes a Synthetic Pulmonary Artery Smooth Muscle Cell Phenotype in Neprilysin Null Mice.

ABSTRACT:

Objective

Pulmonary artery smooth muscle cells (PASMCs) from neprilysin (NEP) null mice exhibit a synthetic phenotype and increased activation of Rho GTPases compared with their wild-type counterparts. Although Rho GTPases are known to promote a contractile SMC phenotype, we hypothesize that their sustained activity decreases SM-protein expression in these cells.

Approach and results

PASMCs isolated from wild-type and NEP^-/- mice were used to assess levels of SM-proteins (SM-actin, SM-myosin, SM22, and calponin) by Western blotting, and were lower in NEP^-/- PASMCs compared with wild-type. Rac and Rho (ras homology family member) levels and activity were higher in NEP^-/- PASMCs, and ShRNA to Rac and Rho restored SM-protein, and attenuated the

SUBMITTER: Karoor V 

PROVIDER: S-EPMC5746466 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature