Hyperglycemia induces abnormal gene expression in hematopoietic stem cells and their progeny in diabetic neuropathy |
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Authors: | Miwako Katagi Tomoya Terashima Junko Okano Hiroshi Urabe Yuki Nakae Nobuhiro Ogawa Jun Udagawa Hiroshi Maegawa Kazuhiro Matsumura Lawrence Chan Hideto Kojima |
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Institution: | 1. Department of Stem Cell Biology and Regenerative Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan;2. Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan;3. Department of Division of Anatomy and Cell Biology, Shiga University of Medical Science, Otsu, Shiga, Japan;4. Department of Critical and Intensive Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan;5. Division of Diabetes, Endocrinology and Metabolism, Departments of Medicine, Molecular and Cellular Biology, and Biochemistry, Baylor College of Medicine, Houston, Texas, United States |
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Abstract: | Diabetic peripheral neuropathy is a major chronic diabetic complication. We have previously shown that in type 1 diabetic streptozotocin-treated mice, insulin- and TNF-α co-expressing bone marrow-derived cells (BMDCs) induced by hyperglycemia travel to nerve tissues where they fuse with nerve cells, causing premature apoptosis and nerve dysfunction. Here we show that similar BMDCs also occur in type 2 diabetic high-fat diet (HFD) mice. Furthermore, we found that hyperglycemia induces the co-expression of insulin and TNF-α in c-kit+Sca-1+lineage− (KSL) progenitor cells, which maintain the same expression pattern in the progeny, which in turn participates in the fusion with neurons when transferred to normoglycemic animals. |
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Keywords: | Neuropathy Hyperglycemia Hematopoietic stem cell Cell&ndash cell fusion Stem cell abnormalities |
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