title: Aqp1 enhances migration of bone marrow mesenchymal stem cells through regulation of FAK and β-catenin.
abstract: Bone marrow mesenchymal stem cells (MSCs) have the potential to migrate to the site of injury and regulate the repair process. Aquaporin 1 (Aqp1) is a water channel molecule and a regulator of endothelial cell migration. To study the role of Apq1 in MSC migration, we manipulated the expression of the Aqp1 gene in MSCs and explored its effects on MSC migration both in vitro and in vivo. Overexpression of Aqp1 promoted MSC migration, while depletion of Aqp1 impaired MSC migration in vitro. When the green fluorescent protein (GFP) labeled Aqp1 overexpressing MSCs were systemically injected into rats with a femoral fracture, there were significantly more GFP-MSCs found at the fracture gap in the Aqp1-GFP-MSC-treated group compared to the GFP-MSC group. To elucidate the underlying mechanism, we screened several migration-related regulators. The results showed that β-catenin and focal adhesion kinase (FAK) were upregulated in the Aqp1-MSCs and downregulated in the Aqp1-depleted MSCs, while C-X-C chemokine receptor type 4 had no change. Furthermore, β-catenin and FAK were co-immunoprecipitated with Aqp1, and depletion of FAK abolished the Aqp1 effects on MSC migration. This study demonstrates that Aqp1 enhances MSC migration ability mainly through the FAK pathway and partially through the β-catenin pathway. Our finding suggests a novel function of Aqp1 in governing MSC migration, and this may aid MSC therapeutic applications.
authors: 1 Department of Orthopaedics and Traumatology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong , Shatin, Hong Kong SAR, People's Republic of China .
authors: Fanbiao
authors: F
authors: Meng
authors: Yunfeng
authors: Y
authors: Rui
authors: Liangliang
authors: L
authors: Xu
authors: Chao
authors: C
authors: Wan
authors: Xiaohua
authors: X
authors: Jiang
authors: Gang
authors: G
authors: Li
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D001861:Bone Regeneration / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000235:genetics; D064987:Cell- and Tissue-Based Therapy; D015536:Down-Regulation; D051417:Focal Adhesion Kinase 1 / Q000096:biosynthesis / Q000378:metabolism*; D050723:Fractures, Bone / Q000235:genetics / Q000628:therapy; D049452:Green Fluorescent Proteins; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D013977:Tibia / Q000166:cytology / Q000293:injuries; D051176:beta Catenin / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: C496022:Aqp1 protein, rat; C486264:Cxcr4 protein, rat; D019718:Receptors, CXCR4; D051176:beta Catenin; D051398:Aquaporin 1; D049452:Green Fluorescent Proteins; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat
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