Li Sung-Chou, Wang Feng-Sheng, Yang Ya-Ling, Tiao Mao-Meng, Chuang Jiin-Haur, Huang Ying-Hsien
Genomics and Proteomics Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 833 Kaohsiung, Taiwan.
Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 833 Kaohsiung, Taiwan.
Int J Mol Sci. 2016 Mar 1;17(3):324. doi: 10.3390/ijms17030324.
Accumulating evidence demonstrates that microRNA-29 (miR-29) expression is prominently decreased in patients with hepatic fibrosis, which consequently stimulates hepatic stellate cells' (HSCs) activation. We used a cDNA microarray study to gain a more comprehensive understanding of genome-wide gene expressions by adjusting miR-29a expression in a bile duct-ligation (BDL) animal model.
Using miR-29a transgenic mice and wild-type littermates and applying the BDL mouse model, we characterized the function of miR-29a with regard to cholestatic liver fibrosis. Pathway enrichment analysis and/or specific validation were performed for differentially expressed genes found within the comparisons.
Analysis of the microarray data identified a number of differentially expressed genes due to the miR-29a transgene, BDL, or both. Additional pathway enrichment analysis revealed that TGF-β signaling had a significantly differential activated pathway depending on the occurrence of miR-29a overexpression or the lack thereof. Furthermore, overexpression was found to elicit changes in Wnt/β-catenin after BDL.
This study verified that an elevated miR-29a level could alleviate liver fibrosis caused by cholestasis. Furthermore, the protective effects of miR-29a correlate with the downregulation of TGF-β and associated with Wnt/β-catenin signal pathway following BDL.
越来越多的证据表明，肝纤维化患者体内的微小RNA-29（miR-29）表达显著降低，这进而刺激肝星状细胞（HSCs）的激活。我们通过在胆管结扎（BDL）动物模型中调节miR-29a的表达，利用cDNA微阵列研究来更全面地了解全基因组基因表达情况。
使用miR-29a转基因小鼠及其野生型同窝小鼠，并应用BDL小鼠模型，我们对miR-29a在胆汁淤积性肝纤维化方面的功能进行了表征。对比较中发现的差异表达基因进行了通路富集分析和/或特异性验证。
微阵列数据分析确定了一些由于miR-29a转基因、BDL或两者共同作用而产生的差异表达基因。进一步的通路富集分析表明，TGF-β信号通路根据miR-29a过表达的有无而有显著不同的激活途径。此外，发现过表达会在BDL后引起Wnt/β-连环蛋白的变化。
本研究证实，升高的miR-29a水平可减轻胆汁淤积引起的肝纤维化。此外，miR-29a的保护作用与TGF-β的下调相关，并与BDL后的Wnt/β-连环蛋白信号通路有关。
