Lin Yingying, Wang Xin, Cui Xinyu, Zhu Na, Li Yanyan, Li Xin
Department of Center of Integrated Traditional Chinese and Western Medicine, Peking University Ditan Teaching Hospital, Beijing, China.
Department of Center of Integrated Traditional Chinese and Western Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Cell Biochem Biophys. 2025 Feb 4. doi: 10.1007/s12013-025-01682-w.
Vitamin A (VA) and its active form, retinoic acid (RA), are crucial for preserving hepatic stellate cells (HSCs) quiescence and reversing fibrosis. While C6orf120 is known to be involved in HSC activation, its role in RA signaling is unclear. This study found that C6orf120 knockdown markedly reduced CCL4-induced liver fibrosis and TGF-β1-induced activation in LX-2 cells, a human HSC line. This inhibition was associated with enhanced RA signaling, particularly affecting the RA receptor beta (RARβ). Inhibition of RARβ significantly reversed the protective effects of C6orf120 knockdown, indicating that RARβ signaling contributes to the inhibitory effect of C6orf120 knockdown on HSC activation. Our results reveal that C6orf120 inhibition could be a therapeutic strategy for liver fibrosis by regulating RARβ signaling.
维生素A（VA）及其活性形式视黄酸（RA）对于维持肝星状细胞（HSC）的静止状态和逆转纤维化至关重要。虽然已知C6orf120参与肝星状细胞激活，但其在RA信号传导中的作用尚不清楚。本研究发现，在人肝星状细胞系LX-2细胞中，敲低C6orf120可显著减轻CCl4诱导的肝纤维化和TGF-β1诱导的激活。这种抑制作用与RA信号增强有关，尤其影响RA受体β（RARβ）。抑制RARβ可显著逆转敲低C6orf120的保护作用，表明RARβ信号传导有助于敲低C6orf120对肝星状细胞激活的抑制作用。我们的研究结果表明，抑制C6orf120可能是一种通过调节RARβ信号传导来治疗肝纤维化的策略。
