LncRNAであるFTXは、Kupffer細胞のM1/M2分極を制御することで、非アルコール性脂肪肝疾患から肝細胞癌への進行を抑制することが明らかになった

LncRNA FTX represses the progression of non-alcoholic fatty liver disease to hepatocellular carcinoma via regulating the M1/M2 polarization of Kupffer cells.

• Huajun Wu
• Zhiwei Zhong
• Anji Wang
• Chunhui Yuan
• Ke Ning
• Huanhuan Hu
• Chao Wang
• Xiangbao Yin

抄録

背景:

非アルコール性脂肪性肝疾患（NAFLD）から肝細胞癌（HCC）への転換に対するlncRNA FTXの効果は不明である。

Background: The effect of lncRNA FTX on non-alcoholic fatty liver disease (NAFLD) conversion to hepatocellular carcinoma (HCC) is unclear.

方法:

Methods: In our study, C57BL/6 mice was fed with high fat diet for obtaining NAFLD mouse model, and diethylnitrosamine induced the formation of HCC tumor. The expression of iNOS and CD206 in tissues were examined using immunohistochemistry. In addition, qRT-PCR was implemented to detect the expression of FTX and mRNAs. The percentage of M1 and M2 Kupffer cells (KCs) were determined using flow cytometry. The pathological change in liver tissues was displayed by H&E staining. Besides, immunofluorescence assay was performed to ensure the primary KCs through labeling F4/80.

結果:

ここでは、NAFLD転化HCC（NAFLD-HCC）患者の肝組織では、NAFLD患者の肝組織に比べてFTXの発現とM1/M2 KCsの比率が低いことを明らかにした。その後、NAFLDがHCCに転換する過程で、FTXの発現とM1/M2 KCs比が低下することを明らかにした。重要なことは、NAFLDからHCCへの転化過程において、FTXの増加はHCC腫瘍の増殖を抑制し、肝障害を改善し、KCsのM1分極を促進したが、FTXのこれらの効果はKCsの不活性化によって逆転したことであった。最後に、in vitro実験では、FTXはKCsのM1分極を促進することが示された。

Results: Here, we found that the expression of FTX and the ratio of M1/M2 KCs in liver tissues from NAFLD-transformed HCC (NAFLD-HCC) patients lower than in liver tissues from NAFLD patients. Subsequently, we revealed that the expression of FTX and M1/M2 KCs ratio were downregulated during NAFLD conversion to HCC. Importantly, increasing of FTX inhibited HCC tumor growth, improved liver damage and promoted M1 polarization of KCs during NAFLD conversion to HCC, while these effects of FTX were reversed by inactivating of KCs. Finally, in vitro experiments, our data indicated that FTX facilitated the M1 polarization of KCs.

結論:

以上の結果から、FTX のアップレギュレーションは NAFLD の HCC 化を抑制するが、KC の M1 分極を促進することが明らかになった。この結果は、NAFLDのHCC化を抑制する新たなバイオマーカーを提供するものであった。

Conclusion: In conclusion, our results demonstrated that upregulation of FTX suppressed NAFLD conversion to HCC though promoting M1 polarization of KCs. Our findings presented a new regulatory mechanism for NAFLD conversion to HCC, and provided a new biomarker for inhibiting this conversion.

© The Author(s) 2020.