Fusion of proinsulin-producing bone marrow-derived cells with hepatocytes in diabetes
Fusion of proinsulin-producing bone marrow-derived cells with hepatocytes in diabetes
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DOI：
10.1073/pnas.0700220104
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发表时间：
2007-03-06
影响因子：
11.1
通讯作者：
Chan, Lawrence
中科院分区：
文献类型：
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作者：
Fujimiya, Mineko;Kojima, Hideto;Chan, Lawrence
我们以前报道过，小鼠糖尿病与肝脏中胰岛素原产生（Proins-P）细胞的出现有关。然而，尚不清楚这些Proins-P骨髓源性细胞（BMDQ）是否仅通过肝脏转运或与肝细胞融合，这通常是极其罕见的事件。在这项研究中，我们发现，在糖尿病中，肝脏中的BMDC不仅产生Proins，而且还产生TNF-α，这表明糖尿病重新编程BMDC中的基因表达，打开“不合适”的基因。使用遗传标记的供体和受体小鼠的骨髓移植显示Proins-P BMDC和肝细胞之间发生融合。接受雄性骨髓移植细胞的雌性小鼠中Proins-P细胞中存在Y染色体进一步支持细胞融合。形态学上，Proins-P融合细胞是产生白蛋白的肝细胞，其构成糖尿病诱导后5个月的肝截面面积的约2.5%。广泛的搜索未能在非糖尿病小鼠中发现任何融合细胞。因此，糖尿病导致Proins-P BMDC与体内肝细胞之间的融合，这一观察结果对糖尿病的病理生理学以及异型细胞融合的基础生物学具有影响。
We previously reported that diabetes in mice is associated with the appearance of proinsulin-producing (Proins-P) cells in the liver. It was unclear, however, whether these Proins-P bone marrow-derived cells (BMDQ merely transit through the liver or undergo fusion with hepatocytes, normally an extremely rare event. In this study, we found that, in diabetes, BMDC in the liver produce not only Proins but also TNF-alpha, suggesting that diabetes reprograms gene expression in BMDC, turning on "inappropriate" genes. Bone marrow transplantation using genetically marked donor and recipient mice showed that fusion occurs between Proins-P BMDC and hepatocytes. Cell fusion is further supported by the presence of the Y chromosome in Proins-P cells in female mice that received male bone marrow transplantation cells. Morphologically, Proins-P fusion cells are albumin-producing hepatocytes that constitute approximate to 2.5% of the liver section area 5 months after diabetes induction. An extensive search failed to reveal any fusion cells in nondiabetic mice. Thus, diabetes causes fusion between Proins-P BMDC and hepatocytes in vivo, an observation that has implications for the pathophysiology of diabetes as well as the fundamental biology of heterotypic cell fusion.