Pulmonary Vascular Disease: Pulmonary Vascular Disease: PAH |

The C-Terminal Tail of Aquaporin 1 Is Required for Hypoxia-Induced Migration and Proliferation of Pulmonary Arterial Smooth Muscle Cells FREE TO VIEW

Ning Lai; Xin Yun; Jian Wang; Larissa Shimoda
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Guangzhou Institute of Respiratory Diseases, Guangzhou, China

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;149(4_S):A514. doi:10.1016/j.chest.2016.02.536
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SESSION TITLE: Pulmonary Vascular Disease: PAH

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM

PURPOSE: Both pulmonary arterial smooth muscle cell (PASMC) proliferation and migration are important contributors to the vascular remodeling that occurs during the development of pulmonary hypertension. We previously demonstrated that aquaporin 1 (AQP1), a member of the water channel family of proteins was expressed in PASMCs and necessary for hypoxia-induced migration; however, the mechanism by which AQP1 controls this response is unclear. The C-terminal tail of AQP1 contains putative calcium (EF-hand) and protein binding sites. Thus, we wanted to explore whether the C-terminal tail or EF-hand motif of AQP1 was required for migration and proliferation.

METHODS: Rat PASMCs were isolated from distal pulmonary arteries, and proliferation and migration were measured using BrdU incorporation and transwell filters, respectively. To deplete AQP1, PASMCs were transfected with AQP1 siRNA (siAQP1) or non-targeting siRNA.

RESULTS: Knockdown of AQP1 reduced basal proliferation and hypoxia-induced migration and proliferation in PASMCs. In subsequent experiments, wild-type AQP1, AQP1 lacking the entire cytoplasmic C-terminal tail or AQP1 with a mutation in the EF-hand motif were expressed in PASMCs using adenoviral constructs. Control cells expressed the same adenoviral construct containing green fluorescent protein. For all AQP1 constructs, infection increased AQP1 protein levels, water permeability and the change in cell volume induced by hypotonic challenge. Infection with wild-type and EF-hand mutated AQP1, but not C-terminal deleted AQP1, increased PASMC migration and proliferation.

CONCLUSIONS: Our results suggest that AQP1 controls both proliferation and migration in PASMCs and that the mechanism requires the C-terminal tail of the protein but is independent of water transport or the EF-hand motif.

CLINICAL IMPLICATIONS: The study provides new information regarding the mechanisms controlling pulmonary arterial smooth muscle cell proliferation and migration, hallmark characteristics of pulmonary hypertension. The role of aquaporin 1 is attributed to the C-terminal tail rather than water transport, providing a novel mechanism for control of cell function.

DISCLOSURE: The following authors have nothing to disclose: Ning Lai, Xin Yun, Jian Wang, Larissa Shimoda

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