OTUD7B controls oxLDL uptake by stabilizing Lox-1 in THP-1 and U937 cells

Background

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.

Results

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.

Conclusions

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.