Protective Role of RNA Helicase DEAD-Box Protein 5 in Smooth Muscle Cell Proliferation and Vascular Remodeling

Rationale: RNA helicases, highly conserved enzymes, are currently believed to be not only involved in RNA modulation, but also in other biological processes. We recently reported that RNA helicase DEAD-box protein 5 (DDX5) is required for maintaining the homeostasis of vascular smooth muscle cells (SMCs). However, the expression and function of RNA helicase in vascular physiology and disease is unknown. Objective: To investigate the role of RNA helicase in vascular diseases. Methods and Results: We showed here that DDX5 was the most abundant DEAD-box protein expressed in human and rodent artery, which mainly located in SMCs. It was demonstrated that DDX5 levels were reduced in cytokine-stimulated SMCs and vascular lesions. DDX5 knocking down or deficiency increased SMC proliferation and migration, while overexpression of DDX5 prevented aberrant proliferation and migration of SMCs. Mechanistic studies revealed transcription factor GATA binding protein 6 (GATA-6) as a novel downstream target of DDX5, which ...