title: Hyperglycemia induces abnormal gene expression in hematopoietic stem cells and their progeny in diabetic neuropathy.
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.
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Miwako
authors.initials: M
authors.lastname: Katagi
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Terashima
authors.affiliation: Department of Division of Anatomy and Cell Biology, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Okano
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Urabe
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakae
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ogawa
authors.affiliation: Department of Division of Anatomy and Cell Biology, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Udagawa
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maegawa
authors.affiliation: Department of Critical and Intensive Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Matsumura
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Departments of Medicine, Molecular and Cellular Biology, and Biochemistry, Baylor College of Medicine, Houston, Texas, United States.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Chan
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan. Electronic address: kojima@belle.shiga-med.ac.jp.
authors.forename: Hideto
authors.initials: H
authors.lastname: Kojima
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D016026:Bone Marrow Transplantation; D002459:Cell Fusion; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D003929:Diabetic Neuropathies / Q000378:metabolism* / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects; D005727:Ganglia, Spinal / Q000473:pathology; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006943:Hyperglycemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007328:Insulin; D014409:Tumor Necrosis Factor-alpha
keywords: Cell–cell fusion; Hematopoietic stem cell; Hyperglycemia; Neuropathy; Stem cell abnormalities