Pathological roles of bone marrow-derived stellate cells in a mouse model of alcohol-induced fatty liver
Pathological roles of bone marrow-derived stellate cells in a mouse model of alcohol-induced fatty liver
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DOI：
10.1152/ajpgi.00055.2009
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发表时间：
2009-09-01
影响因子：
4.5
通讯作者：
Fujimiya, Mineko
中科院分区：
文献类型：
--
作者：
Fujimiya, Tatsuya;Liu, Jinyao;Fujimiya, Mineko
刘军，刘军，刘军，刘志军，刘志军，刘志军，刘志军，刘志军，刘志军，刘志军，刘志军。[J] .中国生物医学工程学报，2009,31(2):451- 456。首次发表于2009年7月16日；doi: 10.1152 / ajpgi.00055.2009。长期饮酒会激活肝星状细胞（hsc），导致肝脏脂肪变性。然而，造血干细胞的来源和肝脏脂肪变化的机制尚未完全阐明。在这里，我们研究了骨髓源性细胞（bmdc）在慢性饮酒小鼠模型中的作用。我们将表达绿色荧光蛋白（GFP）的转基因小鼠骨髓移植到雌性野生型和ROSA小鼠（B6.129S7-Gt 26Sor/J，表达β -半乳糖苷酶的转基因小鼠，β -gal）中，用乙醇（EtOH）处理8或16周。EtOH治疗后，肝脏中表达gfp的BMDCs呈时间依赖性增加。作为对过量饮酒的反应，大约68%的BMDCs成为活化的hsc，因为它们表达α -平滑肌肌动蛋白。同时，约67%和66%的BMDCs分别表达tnf - α和转化生长因子(Tgf)- β 1， RT-PCR中tnf - α和Tgf- β 1 mRNA的过量表达进一步支持了其活性。细胞融合发生在BMDCs和非实质细胞之间，但很少发生在BMDCs和肝细胞之间，β -gal/GFP双染色证实了这一点，y染色体染色进一步支持了这一点。EtOH戒断使大多数由长期饮酒引起的异常正常化。这些结果表明，在酒精诱导的脂肪性肝病小鼠模型中，过量饮酒既刺激骨髓中hsc的归巢，也刺激它们的促纤维化细胞因子的产生。
Fujimiya T, Liu J, Kojima H, Shirafuji S, Kimura H, Fujimiya M. Pathological roles of bone marrow-derived stellate cells in a mouse model of alcohol-induced fatty liver. Am J Physiol Gastrointest Liver Physiol 297: G451-G460, 2009. First published July 16, 2009; doi: 10.1152/ajpgi.00055.2009.-Chronic alcohol consumption activates hepatic stellate cells (HSCs) and causes fatty degeneration in the liver. However, the origin of HSCs and the mechanism of fatty changes of the liver have not been fully elucidated. Here, we examined the roles of bone marrow-derived cells (BMDCs) in a mouse model with chronic alcohol consumption. We performed bone marrow transplantation from transgenic mice expressing green fluorescence protein (GFP) to female wild-type and ROSA mice (B6.129S7-Gt 26Sor/J, transgenic mice expressing beta-galactosidase, beta-gal) and treated them with ethanol (EtOH) for 8 or 16 wk. GFP-expressing BMDCs increased in the liver with EtOH treatment in a time-dependent manner. In response to excess alcohol consumption, approximate to 68% of the BMDCs became activated HSCs in that they expressed alpha-smooth muscle actin. Meanwhile, approximate to 67% and approximate to 66% of these BMDCs expressed Tnf-alpha and transforming growth factor (Tgf)-beta 1, respectively, and the activities were further supported by the excessive mRNA expression of Tnf-alpha and Tgf-beta 1 in RT-PCR, respectively. Cell fusion occurs between BMDCs and nonparenchymal cells but scarcely occurs between BMDCs and hepatocytes, demonstrated by double staining of beta-gal/GFP and further supported by the Y-chromosome staining. The EtOH withdrawal normalized most of the abnormalities produced by chronic alcohol consumption. These results indicate that excess alcohol consumption stimulates both the homing of HSCs from the bone marrow and their profibrogenic cytokine production in a mouse model of alcohol-induced fatty liver disease.