Rosalinda Madonna1, Yong-Jian Geng2, Harnath Shelat3, Peter Ferdinandy4, Raffaele De Caterina5. 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.
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.
Authors: Leili Rohani; Breanna S Borys; Golsa Razian; Pooyan Naghsh; Shiying Liu; Adiv A Johnson; Pranav Machiraju; Heidrun Holland; Ian A Lewis; Ryan A Groves; Derek Toms; Paul M K Gordon; Joyce W Li; Tania So; Tiffany Dang; Michael S Kallos; Derrick E Rancourt Journal: Commun Biol Date: 2020-09-07