Document Detail

The Aquaporin 1 C-terminal Tail is Required for Migration and Growth of Pulmonary Arterial Myocytes.
MedLine Citation:
PMID:  24328827     Owner:  NLM     Status:  Publisher    
Both pulmonary arterial smooth muscle cell (PASMC) proliferation and migration are important contributors to the vascular remodeling that occurs during 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. 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. 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. 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. 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.
Ning Lai; Julie Lade; Kyle Leggett; Xin Yun; Syeda Baksh; Eric Chau; Michael T Crow; Venkataramana Sidhaye; Jian Wang; Larissa A Shimoda
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-12-11
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  -     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2013 Dec 
Date Detail:
Created Date:  2013-12-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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