Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1842, Issue 11, Pages 2266-2275Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2014.07.030
Keywords
Induced pluripotent stem cell; Aquaporin-1; Cytoskeleton remodeling; Hyperosmolarity; Diabetes; Hyperglycemia
Funding
- Istituto Nazionale Ricerche Cardiovascolari (I.N.R.C.)
- Fondazione Cariplo
- Texas Heart Institute
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Background and objective: Hyperglycemia leads to adaptive cell responses in part due to hyperosmolarity. In endothelial and epithelial cells, hyperosmolarity induces aquaporin-1 (AQP1) which plays a role in cytoskeletal remodeling, cell proliferation and migration. Whether such impairments also occur in human induced pluripotent stem cells (iPS) is not known. We therefore investigated whether high glucose-induced hyperosmolarity impacts proliferation, migration, expression of pluripotency markers and actin skeleton remodeling in iPS cells in an AQP1-dependent manner. Methods and results: Human iPS cells were generated from skin fibroblasts by lentiviral transduction of four reprogramming factors (Oct4, Sox2, Klf4, c-Myc). After reprogramming, iPS cells were characterized by their adaptive responses to high glucose-induced hyperosmolarity by incubation with 5.5 mmol/L glucose, high glucose (HG) at 30.5 mM, or with the hyperosmolar control mannitol (HM). Exposure to either HG or HM increased the expression of AQP1. AQP1 co-immunoprecipitated with beta-catenin. HG and HM induced the expression of beta-catenin. Under these conditions, iPS cells showed increased ratios of F-actin to G-actin and formed increased tubing networks. Inhibition of AQP1 with small interfering RNA (siRNA) reverted the inducing effects of HG and HM. Conclusions: High glucose enhances human iPS cell proliferation and cytoskeletal remodeling due to hyperosmolarity-induced upregulation of AQP1. (C) 2014 Elsevier B.V. All rights reserved.
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