Rao Yanbiao, Li Feng, Wan Chao, Tong Shanshan, Fu Yandong, Li Yongsheng
The Fifth Hospital of Xiamen, No. 101 Min'an Road, Xiang'an District, Xiamen, Fujian, 361101, China.
The Fifth Hospital of Xiamen, No. 101 Min'an Road, Xiang'an District, Xiamen, Fujian, 361101, China.
Biochim Biophys Acta Mol Cell Biol Lipids. 2025 Jun;1870(5):159618. doi: 10.1016/j.bbalip.2025.159618. Epub 2025 Apr 26.
The scavenger receptor Lox-1 plays a crucial role in mediating the uptake of oxidized low-density lipoprotein (oxLDL) by macrophages, thereby promoting foam cell formation and the development of atherosclerosis. Recent studies have suggested that ubiquitination plays a role in accelerating the degradation of Lox-1. However, the specific mechanisms underlying how the ubiquitin-proteasome system regulates the stability and function of Lox-1 remain poorly understood.
In our study, we identified OTUD7B, a deubiquitinase, as a potent stabilizer of Lox-1 in THP-1 and U937 cells. Knockdown of OTUD7B significantly reduced the level of Lox-1 and impaired the uptake of oxLDL by these cells. Furthermore, we found that OTUD7B interacts with Lox-1 and deubiquitinates it, thereby promoting its degradation. Importantly, overexpression of Lox-1 effectively rescued oxLDL uptake by OTUD7B-deficient THP-1 and U937 cells.
Our findings indicate that OTUD7B plays a crucial role in controlling oxLDL uptake by enhancing the stability of Lox-1. This highlights the potential significance of targeting the OTUD7B-Lox-1 axis as a therapeutic strategy for atherosclerosis.
清道夫受体Lox-1在介导巨噬细胞摄取氧化型低密度脂蛋白（oxLDL）中起关键作用，从而促进泡沫细胞形成和动脉粥样硬化的发展。最近的研究表明，泛素化在加速Lox-1的降解中起作用。然而，泛素-蛋白酶体系统调节Lox-1稳定性和功能的具体机制仍知之甚少。
在我们的研究中，我们鉴定出去泛素化酶OTUD7B是THP-1和U937细胞中Lox-1的有效稳定剂。敲低OTUD7B可显著降低Lox-1水平，并损害这些细胞对oxLDL的摄取。此外，我们发现OTUD7B与Lox-1相互作用并使其去泛素化，从而促进其降解。重要的是，Lox-1的过表达有效地挽救了OTUD7B缺陷的THP-1和U937细胞对oxLDL的摄取。
我们的研究结果表明，OTUD7B通过增强Lox-1的稳定性在控制oxLDL摄取中起关键作用。这突出了靶向OTUD7B-Lox-1轴作为动脉粥样硬化治疗策略的潜在意义。
