The C‐terminal tail of Aquaporin 1(AQP1) is Required for Migration and Proliferation of Pulmonary Arterial Smooth Muscle Cells (PASMCs)

Abstract

Both PASMC proliferation and migration are important contributors to the vascular remodeling that occurs during the development of pulmonary hypertension. AQP1 is a member of the water channel family of proteins. We previously demonstrated that AQP1 is expressed in and mediates migration and proliferation of PASMCs; however, the mechanism by which AQP1 controls these responses is unclear. The C‐terminal tail of AQP1 contains putative calcium and protein binding sites. Thus, we wanted to explore whether the C‐terminal tail of AQP1 was required for migration and proliferation. Rat PASMCs were harvested from distal pulmonary arteries enzymatically and plated onto culture dishes. Proliferation and migration were measured using BrdU incorporation and transwell filters. PASMCs were treated with 50 ifu/cell for 4 h with an adenoviral construct expressing green fluorescent protein (AdGFP), the control for infection, wild‐type AQP1 (AdAQP1) or AQP1 lacking the entire cytoplasmic C‐terminal tail (AdAQP1CT). Compared to AdGFP cells, infection with AdAQP1 or AdAQP1CT increased total and surface AQP1 protein levels and the rate of change in cell volume in response to hypotonic challenge to a similar level. Infection with AdAQP1, but not AdAQP1CT, increased migration and proliferation. Our results suggest that AQP1 controls proliferation and migration in PASMCs via a mechanism that includes the C‐terminal tail but is independent of water transport.