中科院上海生科院生化與細胞所宋建國研究組研究發(fā)現(xiàn)組蛋白去乙酰化酶1（Histone deacetylase 1,，HDAC1）在轉(zhuǎn)化生長因子-β1 (TGF-β1) 誘導的上皮細胞向間質(zhì)細胞的轉(zhuǎn)變（Epithelial-Mesenchymal Transition,，EMT）過程中發(fā)揮重要作用,。相關(guān)結(jié)果發(fā)表在Int J Biochem Cell Biol雜志上。
組蛋白去乙?；甘且活惸軌虼呋M蛋白以及其它一些蛋白的賴氨酸殘基去乙?；拿福梢愿淖兓虻霓D(zhuǎn)錄狀態(tài)以及信號轉(zhuǎn)導,，調(diào)控相應的生物事件,。目前已經(jīng)報道哺乳動物體內(nèi)的HDACs有18種。其中,，HDAC1在多種生理和病理過程中發(fā)揮了重要的作用,，HDAC1能否調(diào)控肝細胞的EMT過程尚未有報道。
該研究發(fā)現(xiàn)：HDACs的3種結(jié)構(gòu)完全不同的抑制劑均能抑制TGF-β1誘導的小鼠肝細胞的EMT,；過表達HDAC1顯性失活突變體或者利用RNA干擾技術(shù)降低細胞內(nèi)HDAC1（HDAC1 RNAi）的水平亦可抑制TGF-β1誘導的小鼠肝細胞EMT,。 HDAC抑制劑TSA（trichostatin A）以及HDAC1 RNAi也能夠抑制TGF-β1誘導的細胞遷移。研究還表明,，HDAC1可通過抑制ZO-1以及 E-cadherin 的啟動子活性來調(diào)節(jié)TGF-β1誘導的EMT,。此外，還觀察到：HDAC1在多種浸潤性肝癌中有較高的表達,。本研究有助于加深對TGF-β1誘導的EMT的機制的深入了解,，并具有潛在的相關(guān)的醫(yī)學臨床應用參考價值。
該研究項目得到了國家自然科學基金委,、國家科技部及上海市科委的經(jīng)費資助,。(生物谷Bioon.net)
生物谷推薦原文出處：
The International Journal of Biochemistry & Cell Biology doi:10.1016/j.biocel.2010.05.006
Histone deacetylase 1 is required for transforming growth factor-β1-induced epithelial–mesenchymal transition
Weiwei Leia, Kehua Zhanga, Xinchao Pana, Ying Hua, Dongmei Wanga, Xinwang Yuana, Guangwen Shua and Jianguo Song, a,
a Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China
Epithelial–mesenchymal transition (EMT) has been implicated in embryonic development, fibrosis, and tumor metastasis. Histone deacetylases (HDACs) also play important roles in the control of various physiological and pathological events. However, whether HDACs are involved in the control of EMT in liver cells remains unidentified. Three structurally unrelated HDAC inhibitors completely suppress transforming growth factor-β1 (TGF-β1)-induced EMT in AML-12 murine hepatocytes and primary mouse hepatocytes. Expression of a dominant-negative mutant of HDAC1 but not HDAC2 or downregulation of HDAC1 but not HDAC2 by RNAi suppressed TGF-β1-induced EMT. In addition, both HDAC inhibitor TSA and HDAC1 RNAi blocked cell migration. Overexpression of HDAC1 in invasive hepatocellular carcinoma (HCC) samples was detected. Further study showed that the mRNA levels of ZO-1 and E-cadherin were downregulated during TGF-β1-induced EMT, and HDAC1 can downregulate the promoter activities of ZO-1 and E-cadherin. Conclusions: our results demonstrate that HDAC1 is required for TGF-β1-induced EMT and cell migration in hepatocytes. Its high expression levels in majority of invasive HCC samples suggest that, by promoting EMT, HDAC1 can be related with the invasiveness of HCC. The data also suggest that the repression of transcription of ZO-1 and E-cadherin by HDAC1 may be involved in TGF-β1-induced EMT.
