The miR-3074/BMP7 axis regulates TGF-β-caused activation of hepatic stellate cells in vitro and CCl4-caused murine liver fibrosis in vivo

IF 4.3 3区生物学 Human Cell Pub Date : 2024-01-14 DOI:10.1007/s13577-023-01017-y

Bingjie Liu, Xia Xie, Xin Yang, Chengyun Dou, Haibo Tang, Jing Liu

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Abstract

Continuously progressive hepatic fibrosis might cause chronic liver diseases, resulting in hepatic failure. The activation of hepatic stellate cells (HSCs) residing in the liver might induce and influence hepatic fibrosis. In the present study, microRNA 3074 (miR-3074) was found increased within transforming growth factorβ (TGF-β)-activated HSCs and enriched within the TGF-β signaling. In activated HSCs by TGF-β, miR-3074 overexpression aggravated TGF-β-induced fibrotic changes, whereas miR-3074 inhibition exerted opposite effects. miR-3074 directly targeted bone morphogenetic protein 7 (BMP7) and inhibited BMP7 expression. Under TGF-β induction, overexpressed BMP7 notably attenuated the promotive roles of miR-3074 overexpression in TGF-β-activated HSCs. Within carbon tetrachloride (CCl₄)-caused liver fibrosis murine model, miR-3074 agomir administration promoted, while LV-BMP7 administration alleviated CCl₄-induced fibrotic changes; LV-BMP7 significantly attenuated the effects of miR-3074 agomir. Lastly, mmu-miR-3074 also targeted mouse BMP7 and inhibited mouse BMP7 expression. In conclusion, the miR-3074/BMP7 axis regulates TGF-β-caused activation of HSCs in vitro and CCl₄-caused murine liver fibrosis in vivo. BMP7-mediated Smad1/5/8 activation might be involved.

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miR-3074/BMP7 轴调节体外 TGF-β 引起的肝星状细胞活化和体内 CCl4 引起的小鼠肝纤维化

持续进展的肝纤维化可能会引起慢性肝病，导致肝功能衰竭。肝脏中的肝星状细胞（HSCs）的活化可能会诱导和影响肝纤维化。本研究发现，microRNA 3074（miR-3074）在转化生长因子β（TGF-β）激活的造血干细胞中增加，并在 TGF-β 信号转导中富集。在被TGF-β激活的造血干细胞中，过表达miR-3074会加重TGF-β诱导的纤维化变化，而抑制miR-3074则会产生相反的效果。miR-3074直接靶向骨形态发生蛋白7（BMP7）并抑制BMP7的表达。在 TGF-β 诱导下，过表达的 BMP7 明显减弱了 miR-3074 在 TGF-β 激活的造血干细胞中的促进作用。在四氯化碳（CCl4）诱导的肝纤维化小鼠模型中，miR-3074激动剂能促进CCl4诱导的肝纤维化变化，而LV-BMP7能缓解CCl4诱导的肝纤维化变化；LV-BMP7能显著减弱miR-3074激动剂的作用。最后，mmu-miR-3074 还能靶向小鼠 BMP7 并抑制小鼠 BMP7 的表达。总之，miR-3074/BMP7 轴调节体外由 TGF-β 引起的造血干细胞活化和体内由 CCl4 引起的小鼠肝纤维化。BMP7 介导的 Smad1/5/8 激活可能与此有关。

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来源期刊

Human Cell 生物-细胞生物学

CiteScore

6.60

自引率

2.30%

发文量

176

期刊介绍： Human Cell is the official English-language journal of the Japan Human Cell Society. The journal serves as a forum for international research on all aspects of the human cell, encompassing not only cell biology but also pathology, cytology, and oncology, including clinical oncology. Embryonic stem cells derived from animals, regenerative medicine using animal cells, and experimental animal models with implications for human diseases are covered as well. Submissions in any of the following categories will be considered: Research Articles, Cell Lines, Rapid Communications, Reviews, and Letters to the Editor. A brief clinical case report focusing on cellular responses to pathological insults in human studies may also be submitted as a Letter to the Editor in a concise and short format. Not only basic scientists but also gynecologists, oncologists, and other clinical scientists are welcome to submit work expressing new ideas or research using human cells.