解放军医学院,解放军302医院感染性疾病诊疗与研究中心,军事医学科学院野战输血研究所干细胞与再生医学研究室,解放军302医院感染性疾病诊疗与研究中心,解放军302医院感染性疾病诊疗与研究中心,军事医学科学院野战输血研究所干细胞与再生医学研究室,解放军302医院感染性疾病诊疗与研究中心,解放军302医院感染性疾病诊疗与研究中心,军事医学科学院野战输血研究所干细胞与再生医学研究室,解放军302医院感染性疾病诊疗与研究中心
国家自然科学基金资助项目(81200303, 81470097)
Medical School of Chinese PLA,Treatment and Research Center of Infectious Diseases ,Beijing 302 Hospital,Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine,Treatment and Research Center of Infectious Diseases ,Beijing 302 Hospital,Treatment and Research Center of Infectious Diseases ,Beijing 302 Hospital,Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine,Treatment and Research Center of Infectious Diseases ,Beijing 302 Hospital,Treatment and Research Center of Infectious Diseases ,Beijing 302 Hospital,Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine,Treatment and Research Center of Infectious Diseases ,Beijing 302 Hospital
This work was supported by a grant from The National Natural Science Foundation of China (81200303, 81470097)
肝星状细胞是肝脏中重要的间质细胞,是肝细胞外基质的主要来源.表皮形态发生素(epimorphin、EPM、syntaxin2)在肝脏发育、再生及癌变过程中发挥了重要的作用,目前其表达变化的调控机制及对肝星状细胞的作用还未有报道.通过对肝组织标本进行检测,发现肝纤维化过程中肝星状细胞表达EPM上调.从表观遗传学的角度对EPM表达变化调控机制进行研究,发现DNA去甲基化促进了EPM的表达.为了研究EPM对肝星状细胞的可能的调节作用,将EPM表达质粒转染肝星状细胞,之后检测了EPM对肝星状细胞增殖及迁移能力的变化.结果证明EPM能够促进肝星状细胞的增殖与迁移.本研究发现,激活的肝星状细胞高表达EPM可能是由于DNA去甲基化引起的,同时,高表达的EPM能够促进肝星状细胞的增殖与迁移,进而促进肝纤维化进展.
Hepatic stellate cell(HSC), an important interstitial cell in the liver, is the main source of extracellular matrix. Epimorphin (EPM, also called syntaxin2), a mesenchymal cell surface-associated molecule expressed in HSC, has been reported that the dysfunction is related to the development, regeneration and carcinogenesis of the liver. We found that the expression of EPM was up-regulated in hepatic stellate cells in the process of hepatic fibrosis. We studied the mechanism of EPM expression changes, found that the demethylation of promoter region promoted the expression of EPM. Stable EPM-overexpression transgenic cell lines were generated by transfecting human hepatic stellate cells with plasmids. Reverse transcriptase polymerase chain reaction(PCR) analyses and Westen blot indicated that the mRNA and protein levels of EPM in the transgenic cell lines were significantly up-regulated than that in control. By MTT assay and transwell motility assay, we further confirmed that EPM induced HSC proliferation and invasion. In conclusion, the high expression of EPM in activated hepatic stellate cells is caused by DNA demethylation, and EPM can promote the proliferation and migration of hepatic stellate cells, it may be involved in hepatic fibrogenesis.
石 磊,秦恩强,贾雅丽,吴丹,金磊,曾泉,姜天俊,聂为民,岳文,王福生.肝星状细胞中表皮形态发生素表达调控机制及其作用研究[J].生物化学与生物物理进展,2016,43(5):506-513
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