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基于miRNA-204/NUAK1/Hippo信号轴研究红花总黄酮抑制肝星状细胞活化的作用
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| 篇名： | 基于miRNA-204/NUAK1/Hippo信号轴研究红花总黄酮抑制肝星状细胞活化的作用 |
| TITLE： | Effects of total flavonoids from Carthamus tinctorius L. on hepatic stellate cell activation based on miRNA-204/NUAK1/Hippo signaling axis |
| 摘要： | 目的 基于微RNA（miRNA）-204/NUAK家族SNF1样激酶1（NUAK1）/Hippo信号轴研究红花总黄酮（TFCTL）抑制肝星状细胞（HSC）活化的作用，为进一步阐明TFCTL抗肝纤维化的作用机制提供参考。方法将HSC-T6细胞分为对照组、模型组、TFCTL低浓度组（20μg/mL）、TFCTL中浓度组（40μg/mL）、TFCTL高浓度组（60μg/mL）。除对照组外，其余各组均加入5ng/mL的转化生长因子β诱导HSC活化，然后加入相应药液/培养基培养24h。培养结束后，检测细胞凋亡情况以及细胞中α-平滑肌肌动蛋白（α-SMA）、Ⅰ型胶原蛋白（CollagenⅠ）和Hippo/Yes相关蛋白（YAP）通路相关蛋白[YAP、大肿瘤抑制激酶1（LATS1）、哺乳动物STE20样激酶1（MST1）]表达。另采用细胞转染法从基因、蛋白层面分别考察TFCTL对miRNA-204/NUAK1/Hippo信号轴活性的影响。结果经TFCTL干预后，HSC-T6细胞凋亡率和细胞中MST1（TFCTL高浓度组除外）、LATS1蛋白表达水平均显著升高（P＜0.05），细胞中α-SMA、CollagenⅠ、YAP（TFCTL中浓度组除外）蛋白表达水平均显著降低（P＜0.05）。进一步的细胞转染实验结果显示，转染miRNA-204模拟物后，HSC-T6细胞中α-SMA、CollagenⅠ、NUAK1、YAPmRNA及其蛋白表达水平均显著降低（P＜0.05），LATS1mRNA及其蛋白表达水平、MST1mRNA表达水平均显著升高（P＜0.05），且转染miRNA-204抑制剂后的结果与之相反（MST1mRNA除外）。结论TFCTL可通过上调miRNA-204表达，下调NUAK1表达，抑制Hippo/YAP通路活性，从而抑制HSC活化并促进其凋亡，进而发挥抗肝纤维化作用。 |
| ABSTRACT： | OBJECTIVE To investigate the effects of total flavonoids from Carthamus tinctorius L. （TFCTL） on hepatic stellate cell （HSC） activation based on the microRNA （miRNA）-204/NUAK family SNF1-like kinase 1 （NUAK1）/Hippo signaling axis， thereby elucidating the potential mechanism underlying their antifibrotic effects. METHODS The HSC-T6 cells were divided into control group， model group， TFCTL low-concentration group （20 μg/mL）， TFCTL medium-concentration group （40 μg/mL）， and TFCTL high-concentration group （60 μg/mL）. Except for control group， the remaining groups were treated with 5 ng/mL of transforming growth factor-β to induce the activation of hepatic stellate cells， followed by the addition of corresponding drug solutions/culture medium and incubation for 24 hours. Cell apoptosis was assessed， the expression levels of α-smooth muscle actin （α-SMA）， type Ⅰ collagen （Collagen Ⅰ） and proteins associated with the Hippo/Yes-associated protein （YAP） pathway [YAP， large tumor suppressor kinase 1 （LATS1）， and mammalian STE20-like kinase 1 （MST1）] were detected. Additionally， cell transfection was used to investigate the activity of the miRNA-204/NUAK1/Hippo signaling axis at both the genetic and protein levels. RESULTS After intervention with TFCTL， the apoptosis rate of HSC-T6 cells and the protein expressions of MST1 （except for the TFCTL high-concentration group） and LATS1 were significantly increased （P＜0.05）， while the protein expressions of α-SMA， CollagenⅠ， and YAP （except for the TFCTL medium-concentration group） were significantly decreased （P＜0.05）. Further results from cell transfection experiments revealed that after transfection with miRNA-204 mimics， the mRNA it’s protein expressions of α-SMA， CollagenⅠ， NUAK1， and YAP in HSC-T6 cells were significantly decreased （P＜0.05）， while the mRNA and protein expressions of LATS1 and the mRNA expression of MST1 were significantly increased （P＜0.05）. Conversely， the results were opposite following transfection with miRNA-204 inhibitors. CONCLUSIONS TFCTL can exert anti-hepatic fibrosis effects by up-regulating the expression of miRNA-204， thereby down- regulating the expressions of NUAK1， inactivating the Hippo/YAP pathway， which in turn suppresses the activation of HSC and promotes their apoptosis. |
| 期刊： | 2026年第37卷第03期 |
| 作者： | 李明奇；赵晓璐；张晨璐；王映荷；马月宏 |
| AUTHORS： | LI Mingqi，ZHAO Xiaolu，ZHANG Chenlu，WANG Yinghe，MA Yuehong |
| 关键字： | 红花总黄酮；miRNA-204/NUAK1/Hippo信号轴；Hippo/YAP通路；肝星状细胞；肝纤维化；凋亡 |
| KEYWORDS： | total flavonoids from Carthamus tinctorius L.； miRNA-204/NUAK1/Hippo signaling axis； Hippo/YAP pathway； |
| 阅读数： | 2 次 |
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