title: Aquaporin-1 plays important role in proliferation by affecting cell cycle progression.
abstract: Aquaporin-1 (AQP1) has been associated with tumor development. Here, we investigated how AQP1 may affect cell proliferation. The proliferative rate of adult carotid body (CB) cells, known to proliferate under chronic hypoxia, was analyzed in wild-type (AQP1(+/+) ) and knock out (AQP1(-/-) ) mice, maintained in normoxia or exposed to hypoxia while BrdU was administered. Fewer numbers of total BrdU(+) and TH-BrdU(+) cells were observed in AQP1(-/-) mice, indicating a role for AQP1 in CB proliferation. Then, by flow cytometry, cell cycle state and proliferation of cells overexpressing AQP1 were compared to those of wild-type cells. In the AQP1-overexpressing cells, we observed higher cell proliferation and percentages of cells in phases S and G2/M and fewer apoptotic cells after nocodazole treatment were detected by annexin V staining. Also in these cells, proteomic assays showed higher expression of cyclin D1 and E1 and microarray analysis revealed changes in many cell proliferation-related molecules, including, Zeb 2, Jun, NF-kβ, Cxcl9, Cxcl10, TNF, and the TNF receptor. Overall, our results indicate that the presence of AQP1 modifies the expression of key cell cycle proteins apparently related to increases in cell proliferation. This contributes to explaining the presence of AQP1 in many different tumors.
authors.affiliation: Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla (Departamento de Fisiología Médica y Biofísica), Seville, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Galán-Cobo
authors.affiliation: Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla (Departamento de Fisiología Médica y Biofísica), Seville, Spain.
authors.forename: Reposo
authors.initials: R
authors.lastname: Ramírez-Lorca
authors.affiliation: Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla (Departamento de Fisiología Médica y Biofísica), Seville, Spain.|Biomedical Research Centre Network for Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Toledo-Aral
authors.affiliation: Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla (Departamento de Fisiología Médica y Biofísica), Seville, Spain.|Biomedical Research Centre Network for Respiratory Diseases (CIBERES), Madrid, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Echevarría
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism*; D002344:Carotid Body / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology*; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: C496021:Aqp1 protein, mouse; D012333:RNA, Messenger; D051398:Aquaporin 1