脂质纳米颗粒携带的 miR-29c 在肾脏纤维化中介导 TGF-β 信号通路

IF 2.9 4区 医学 Q1 Medicine Journal of biomedical nanotechnology Pub Date : 2023-11-01 DOI:10.1166/jbn.2023.3711
Yuting Gong, Yumei Liang, Yinyin Chen, Ying Chen, Qinghua Zeng, Shuyi Qian
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引用次数: 0

摘要

miR-29c 与肾脏纤维化有关脂质纳米颗粒可抑制细胞生长。本研究主要探讨脂质纳米颗粒携带的miR-29c是否可能调控TGF-β信号的表达,进而参与肾脏纤维化。用20 μmol/L miR-29c脂质纳米颗粒干预肾脏纤维化细胞HK-2,然后分析HK-2细胞的增殖数量和细胞周期变化、TGF-β通路蛋白的表达以及TGF-β与miR-29c的关系。给小鼠注射 Ang II(1000 ng/kg/min)4 周,以建立小鼠肾脏纤维化模型。用脂质纳米颗粒携带的 miR-29c 和 PBS 处理小鼠后,测定肾纤维化的变化和 TGF-β 的表达。脂质纳米颗粒携带的miR-29c浓度越高,细胞增殖下降越明显,S期细胞开始显著下降(P<0.05)。脂质纳米颗粒+PBS组细胞数量最少,PBS组和脂质纳米颗粒+TGF-β抑制剂组细胞数量较多。 TGF-β 是 miR-29c 的靶基因。当纳米脂质乳液中的miR-29c浓度为20 μmol/L时,TGF-β蛋白的表达量减少。 载有miR-29c的纳米脂质颗粒能显著减轻Ang II引起的肾损伤。与对照组小鼠相比,TGF-β在肾脏纤维化细胞中高表达,脂质纳米颗粒处理后TGF-β的表达下降。 脂质纳米颗粒携带的miR-29c能抑制肾脏纤维化细胞的增殖,调控TGF-β通路,最终控制异常细胞增殖。
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miR-29c Carried by Lipid Nanoparticles Mediates TGF-β Signaling Pathway in Renal Fibrosis
miR-29c is related to renal fibrosis. Lipid nanoparticles can inhibit cell growth. This study mainly explores whether miR-29c carried by lipid nanoparticles may regulate the expression of TGF-β signaling and then involves in renal fibrosis. Kidney fibrosis cells HK-2 were intervened with 20 μmol/L miR-29c carried by lipid nanoparticles followed by analysis of the proliferation number and cell cycle changes of HK-2 cells, expression of TGF-β pathway protein, and relationship between TGF-β and miR-29c. Mice were infused with Ang II (1000 ng/kg/min) for 4 weeks to establish a mouse model of renal fibrosis. After treatment with miR-29c carried by lipid nanoparticles and PBS, the changes of renal fibrosis and the expression of TGF-β were measured. The higher the concentration of miR-29c carried by lipid nanoparticles, the more significant the decrease in cell proliferation, and cells in S phase began to decline significantly (P <0.05). Cell number in lipid nanoparticle+PBS group was the lowest and cells in PBS group and lipid nanoparticle+TGF-β inhibitor group were higher. TGF-β is a target gene of miR-29c. When the concentration of miR-29c in lipid nanoemulsion was 20 μmol/L, the expression of TGF-β protein decreased. miR-29c-carried lipid nanoparticles significantly attenuated Ang II-induced kidney injury. TGF-β was highly expressed in renal fibrosis compared with control mice and the expression of TGF-β was decreased after lipid nanoparticle treatment. miR-29c carried by lipid nanoparticles can inhibit the proliferation of renal fibrosis cells, regulate the TGF-β pathway, and ultimately control abnormal cell proliferation.
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CiteScore
4.30
自引率
17.20%
发文量
145
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2.3 months
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