The Effect of Low-Density Lipoprotein Receptor-Related Protein-1 on Acute Kidney Injury and Renal Tubular Epithelial Triglyceride Accumulation.

Introduction: Various types of acute kidney injury (AKI) are associated with triglyceride (TG) accumulation in renal tubular epithelial cells, but the role and mechanisms of TG accumulation in AKI remain unclear. This study aimed to explore the impact of low-density lipoprotein (LDL) receptor-related protein-1 (LRP1), a protein that mediates TG endocytosis, on ischemia-reperfusion injury (IRI)-induced AKI and TG accumulation in renal tubular epithelial cells.

Methods: We established an IRI-induced AKI mouse model and assessed LRP1 expression by Western blot, RT-qPCR, and immunofluorescence. The LRP1 antagonist receptor-associated protein (RAP) was used to evaluate the effect of LRP1 on AKI and renal TG accumulation in the AKI mouse model. We applied a carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-induced hypoxia-reoxygenation model to HK-2 cells in vitro. The effects of very low-density lipoproteins (VLDLs) and LRP1 silencing on TG levels, cell viability, and apoptosis in HK-2 cells were observed.

Results: We observed significant TG accumulation in renal tissue during IRI-AKI, accompanied by upregulation of LRP1 in renal tubular epithelial cells. After intervention with the LRP1 antagonist RAP, AKI was significantly alleviated, and TG levels in renal tissue were notably reduced. However, in the in vitro model, although VLDL increased TG levels in HK-2 cells in both normal culture and hypoxia-reoxygenation conditions, it did not alleviate the decrease in cell viability induced by CCCP. In the absence of exogenous VLDL, silencing LRP1 still reduced CCCP-induced TG accumulation and cell apoptosis, although the reduction in TG levels was less pronounced compared to the presence of exogenous VLDL.

Conclusion: Our study demonstrated that the increased expression of LRP1 on renal tubular epithelial cells contributes to IRI-induced AKI and TG accumulation. The injury effects of LRP1 on the renal tubules are independent of TG endocytosis. Targeting the inhibition of LRP1 may emerge as a novel therapeutic strategy for AKI.