The C‐terminal tail of aquaporin 1 modulates β‐catenin expression in pulmonary arterial smooth muscle cells (1175.2)

PASMC proliferation and migration are important contributors to the vascular remodeling that occurs during hypoxic pulmonary hypertension. Hypoxia increases the expression of AQP1, a member of the water channel family of proteins, in rat PASMCs and we previously showed that AQP1 controls proliferation and migration in PASMCs via a mechanism that includes the C‐terminal tail but is independent of water transport. β‐catenin, part of the Wnt signaling pathway, activates the transcription of crucial target genes controlling proliferation. In melanoma and endothelial cells, Lin‐7, a cell junction protein, interacts with AQP1 to regulate β‐catenin levels. Thus, we explored whether β‐catenin, Lin‐7 and AQP1 interact in PASMCs and, if so, whether the C‐terminal tail of AQP1 was required. Rat PASMCs were harvested, plated onto culture dishes and infected with adenoviral constructs expressing green fluorescent protein (AdGFP), the control for infection, wild‐type AQP1 (AdAQP1) or AQP1 lacking the cytoplasmic C‐terminal tail (AdAQP1CT). Compared to AdGFP cells, infection with AdAQP1, but not AdAQP1CT, increased PASMC migration and proliferation and β‐catenin protein expression. Interestingly, immunoblot analysis revealed that Lin‐7 was not expressed in rat PASMCs. Our results suggest that increased AQP1 levels upregulate β‐catenin protein levels via a mechanism requiring the AQP1 C‐terminal tail but independent of Lin‐7. Grant Funding Source : AHA0755479