Homing of the bone marrow-derived interstitial cells of Cajal is decreased in diabetic mouse intestine.
BACKGROUND
Interstitial cells of Cajal (ICCs), which express c-Kit receptor tyrosine kinase (KIT), play an important role in gastrointestinal motility. Loss of ICCs likely contributes to diabetic gastrointestinal motility disorder, however, the mechanism of attrition remains unknown. Here, we test the hypothesis that the bone marrow-derived progenitors are an important source of intestinal ICCs and that decreased homing of these progenitors in diabetes contributes to ICC diminution.


METHODS
Wild type mice were X-ray irradiated, transplanted with bone marrow (BMT) from green fluorescence protein (GFP)-transgenic (TG)-mice and subsequently made diabetic by streptozotocin (STZ) injection. Intestinal homing of GFP-positive bone marrow-derived cells was examined 2 or 5 months after STZ treatment.


RESULTS
In the BMT-mice, we found many GFP-positive bone marrow-derived cells (BMDCs) in most parts of the intestinal area, the number of BMDCs was significantly decreased in diabetic mice compared with nondiabetic controls. As a representative area, we further examined the myenteric plexus of the proximal small intestine, and found that the cell numbers of ICCs marked by c-Kit-positive immunoreactivity were decreased by more than 40% in diabetic versus nondiabetic mice. Furthermore, numbers of c-Kit+/GFP+ and c-Kit+/GFP- cells were similar in nondiabetic mice, and decreased by 45.8% and 42.0%, respectively, in diabetic mice.


CONCLUSIONS
These results suggest that the decreased homing from the bone marrow is a major cause of ICC loss in the intestine in diabetes mellitus.
Department of Molecular Genetics in Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
Yimin
Y
Li
Hideto
H
Kojima
Kazunori
K
Fujino
Kazuhiro
K
Matsumura
Miwako
M
Katagi
Hiroshi
H
Urabe
Lawrence
L
Chan
Yutaka
Y
Eguchi
Linghui
L
Zhao
Hiroshi
H
Kimura
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002465:Cell Movement; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology*; D005260:Female; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D007150:Immunohistochemistry; D056885:Interstitial Cells of Cajal / Q000378:metabolism / Q000473:pathology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000294:innervation / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009197:Myenteric Plexus / Q000378:metabolism / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D014916:Whole-Body Irradiation
D049452:Green Fluorescent Proteins; D019009:Proto-Oncogene Proteins c-kit
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