細(xì)胞凋亡和上皮細(xì)胞向間質(zhì)細(xì)胞的轉(zhuǎn)變 (Epithelial-Mesenchymal Transition,，EMT) 在多種生理和病理過程中起到了重要的作用。細(xì)胞凋亡和EMT的失調(diào)會導(dǎo)致一些疾病的發(fā)生,，例如腫瘤的形成和轉(zhuǎn)移、肝臟和腎臟纖維化和胚胎發(fā)育的異常等,。中國科學(xué)院上海生命科學(xué)研究院生物化學(xué)與細(xì)胞生物學(xué)研究所宋建國研究組在10月發(fā)表的Hepatology上報道了一氧化氮調(diào)控TGF-β1誘導(dǎo)的細(xì)胞凋亡和上皮細(xì)胞向間質(zhì)細(xì)胞轉(zhuǎn)變的作用及相關(guān)機(jī)制,。
在小鼠肝實(shí)質(zhì)細(xì)胞中，轉(zhuǎn)化生長因子-β1(Transforming Growth Factor-β,，TGF-β1) 可以同時誘導(dǎo)細(xì)胞凋亡和EMT兩種生物學(xué)過程,。一氧化氮 (Nitric Oxide, NO) 是一種具有高度反應(yīng)活性的氣體小分子，參與調(diào)節(jié)肝臟的多種生理病理過程,，對肝臟具有重要的保護(hù)作用,。研究發(fā)現(xiàn)：加入外源的NO供體，可以抑制TGF-β1誘導(dǎo)的肝細(xì)胞凋亡和EMT,。通過細(xì)胞轉(zhuǎn)染和細(xì)胞內(nèi)誘導(dǎo)表達(dá)等方法提高誘導(dǎo)性NO合成酶（iNOS）的表達(dá)和內(nèi)源性NO的生成,，也可以抑制TGF-β1誘導(dǎo)的肝細(xì)胞凋亡和EMT，從而進(jìn)一步證實(shí)了NO的作用,。進(jìn)一步的研究工作顯示NO可以通過下調(diào)細(xì)胞內(nèi)ATP水平和抑制STAT3活化抑制TGF-β1誘導(dǎo)的肝細(xì)胞凋亡和EMT,。本研究有助于加深對TGF-β1和NO調(diào)控細(xì)胞凋亡和EMT的機(jī)制的認(rèn)識，并具有潛在的相關(guān)的醫(yī)學(xué)臨床應(yīng)用參考價值,。
該項研究工作得到了科技部,、基金委 、中國科學(xué)院和上海市科委的經(jīng)費(fèi)支持,。（生物谷Bioon.com）
生物谷推薦原始出處：
Hepatology DOI:10.1002/hep.23156
Nitric oxide suppresses transforming growth factor-1-induced epithelial-to-mesenchymal transition and apoptosis in mouse hepatocytes
Xinchao Pan, Xunde Wang, Weiwei Lei, Lihua Min, Yanan Yang, Xin Wang, Jianguo Song *
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, P.R. China
Nitric oxide (NO) is a multifunctional regulator that is implicated in various physiological and pathological processes. Here we report that administration of NO donor S-nitroso-N-acetylpenicillamine (SNAP) inhibited transforming growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) and apoptosis in mouse hepatocytes. Overexpression of inducible NO synthase (iNOS) by transfection of the iNOS-expressing vector, which increased NO production, also inhibited the TGF-β1-induced EMT and apoptosis in these cells. Treatment of cells with proinflammatory mediators, including tumor necrosis factor (TNF)-, interleukin (IL)-β1, and interferon (IFN)-β, which increased the endogenous NO production, produced the same inhibitory effect. Furthermore, exogenous NO donor SNAP treatment caused a decrease in the intracellular adenosine triphosphate (ATP) levels. Consistently, depletion of intracellular ATP by mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) inhibited the TGF-β1-induced EMT and apoptosis, suggesting that an NO-induced decrease of ATP involved in the NO-mediated inhibition of TGF-1-induced EMT and apoptosis. NO and FCCP also inhibited TGF-1-induced STAT3 activation, suggesting that signal transducer and activator of transcription 3 inactivation is involved in the NO-induced effects on TGF-1-induced EMT and apoptosis. Conclusion: Our study indicates that NO plays an important role in the inhibition of TGF-1-induced EMT and apoptosis in mouse hepatocytes through the downregulation of intracellular ATP levels. The data provide an insight into the in vivo mechanisms on the function of NO during the processes of both EMT and apoptosis. (HEPATOLOGY 2009.)
