title: Ablation of a small subpopulation of diabetes-specific bone marrow-derived cells in mice protects against diabetic neuropathy.
abstract: Diabetic peripheral neuropathy (DPN) is a major diabetic complication. Previously, we showed that hyperglycemia induces the appearance of proinsulin (PI)-producing bone marrow-derived cells (PI-BMDCs), which fuse with dorsal root ganglion neurons, causing apoptosis, nerve dysfunction, and DPN. In this study, we have devised a strategy to ablate PI-BMDCs in mice in vivo. The use of this strategy to selectively ablate TNFα-producing PI-BMDCs in diabetic mice protected these animals from developing DPN. The findings provide powerful validation for a pathogenic role of PI-BMDCs and identify PI-BMDCs as an accessible therapeutic target for the treatment and prevention of DPN.
authors.affiliation: Division of Diabetes, Endocrinology, and Metabolism and the Diabetes Research Center, Departments of Medicine, Molecular and Cellular Biology, Biochemistry, and Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas; and.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Urabe
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Terashima
authors.affiliation: Division of Diabetes, Endocrinology, and Metabolism and the Diabetes Research Center, Departments of Medicine, Molecular and Cellular Biology, Biochemistry, and Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas; and Department of Stem Cell Biology and Regenerative Medicine, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, Japan.
authors.forename: Hideto
authors.initials: H
authors.lastname: Kojima
authors.affiliation: Division of Diabetes, Endocrinology, and Metabolism and the Diabetes Research Center, Departments of Medicine, Molecular and Cellular Biology, Biochemistry, and Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas; and lchan@bcm.edu.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Chan
mesh_terms: D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D003929:Diabetic Neuropathies / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D005727:Ganglia, Spinal / Q000166:cytology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D051379:Mice; D008822:Mice, Transgenic; D009431:Neural Conduction / Q000235:genetics* / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C514817:Ins1 protein, mouse; C561967:Ins2 protein, mouse; D007328:Insulin; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha
keywords: bone marrow-derived cells; diabetic peripheral neuropathy; diphtheria toxin; diphtheria toxin receptor; dorsal root ganglion; proinsulin; tumor necrosis factor-α