The fusion of bone-marrow-derived proinsulin-expressing cells with nerve cells underlies diabetic neuropathy.
Diabetic neuropathy is the most common microvascular complication of diabetes. Here we show that, in streptozotocin-induced diabetic rodents with neuropathy, a subpopulation of bone-marrow-derived cells marked by proinsulin expression migrates to and fuses with neurons in the sciatic nerve and dorsal root ganglion (DRG), resulting in neuronal dysfunction and accelerated apoptosis. The absence or presence of proinsulin expression, which identifies the fusion cells, and not the disease state (nondiabetic vs. diabetic) of the rats from which the DRG neurons are isolated determines whether the DRG neurons show normal or abnormal calcium homeostasis and apoptosis. These results suggest that bone-marrow-derived cells may play an important role in the pathogenesis of diabetic complications.
Terashima
Tomoya
T
Department of Molecular Genetics in Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
Kojima
Hideto
H
Fujimiya
Mineko
M
Matsumura
Kazuhiro
K
Oi
Jiro
J
Hara
Manami
M
Kashiwagi
Atsunori
A
Kimura
Hiroshi
H
Yasuda
Hitoshi
H
Chan
Lawrence
L
D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D002118:Calcium / Q000378:metabolism; D002459:Cell Fusion; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003929:Diabetic Neuropathies / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006706:Homeostasis; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D011123:Polyploidy; D011384:Proinsulin / Q000096:biosynthesis* / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000378:metabolism / Q000473:pathology; D014184:Transplantation, Homologous
D012333:RNA, Messenger; D011384:Proinsulin; D002118:Calcium