Department of Molecular Genetics in Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
J Gastroenterol Hepatol. 2011 Jun;26(6):1072-8. doi: 10.1111/j.1440-1746.2011.06670.x.
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.
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.
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.
These results suggest that the decreased homing from the bone marrow is a major cause of ICC loss in the intestine in diabetes mellitus.
表达 c-Kit 受体酪氨酸激酶（KIT）的 Cajal 间质细胞（ICCs）在胃肠动力中发挥重要作用。ICCs 的缺失可能导致糖尿病性胃肠动力障碍，但其衰减机制尚不清楚。在这里，我们检验了以下假说，即骨髓源性祖细胞是肠 ICCs 的重要来源，并且这些祖细胞在糖尿病中的归巢减少导致 ICC 减少。
野生型小鼠接受 X 射线照射，接受来自绿色荧光蛋白（GFP）转基因（TG）小鼠的骨髓（BMT）移植，然后通过链脲佐菌素（STZ）注射使其发生糖尿病。在 STZ 处理后 2 或 5 个月检查 GFP 阳性骨髓源性细胞的肠归巢。
在 BMT 小鼠中，我们发现大多数肠区域都有许多 GFP 阳性骨髓源性细胞（BMDCs），与非糖尿病对照相比，糖尿病小鼠中的 BMDC 数量明显减少。作为代表性区域，我们进一步检查了近端小肠的肌间神经丛，发现 c-Kit 阳性免疫反应性 ICCs 的细胞数量在糖尿病小鼠中减少了 40%以上。此外，c-Kit+/GFP+和 c-Kit+/GFP-细胞在非糖尿病小鼠中的数量相似，而在糖尿病小鼠中分别减少了 45.8%和 42.0%。
这些结果表明，骨髓归巢减少是糖尿病中肠 ICC 缺失的主要原因。
