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Biochim Biophys Acta. 2014 Nov;1842(11):2266-75. doi: 10.1016/j.bbadis.2014.07.030. Epub 2014 Aug 7.

High glucose-induced hyperosmolarity impacts proliferation, cytoskeleton remodeling and migration of human induced pluripotent stem cells via aquaporin-1.

Author information

1
Heart Failure Research, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, TX, USA; Institute of Cardiology, Department of Neuroscience and Imaging, "G. d'Annunzio" University, Chieti, Italy.
2
Heart Failure Research, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, TX, USA; Department of Internal Medicine, Division of Cardiology, The University of Texas Health Science Center at Houston, Houston, TX, USA.
3
Heart Failure Research, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, TX, USA.
4
Pharmahungary Group, Szeged, Hungary; Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
5
Institute of Cardiology, Department of Neuroscience and Imaging, "G. d'Annunzio" University, Chieti, Italy. Electronic address: rdecater@unich.it.

Abstract

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 5.5mmol/L glucose, high glucose (HG) at 30.5mM, or with the hyperosmolar control mannitol (HM). Exposure to either HG or HM increased the expression of AQP1. AQP1 co-immunoprecipitated with β-catenin. HG and HM induced the expression of β-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.

KEYWORDS:

Aquaporin-1; Cytoskeleton remodeling; Diabetes; Hyperglycemia; Hyperosmolarity; Induced pluripotent stem cell

PMID:
25108283
DOI:
10.1016/j.bbadis.2014.07.030
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